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Introduction: Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in the sensory ganglia and disseminates to these sites remain unclear. Methods: We combined a single-cell sequencing approach and a well-established rhesus macaque experimental model using Simian varicella virus (SVV), which recapitulates the VZV infection in humans, to define the acute immune response to SVV in the lung as well as compare the transcriptome of infected and bystander lung-resident T cells and macrophages. Results and discussion: Our analysis showed a decrease in the frequency of alveolar macrophages concomitant with an increase in that of infiltrating macrophages expressing antiviral genes as well as proliferating T cells, effector CD8 T cells, and T cells expressing granzyme A (GZMA) shortly after infection. Moreover, infected T cells harbored higher numbers of viral transcripts compared to infected macrophages. Furthermore, genes associated with cellular metabolism (glycolysis and oxidative phosphorylation) showed differential expression in infected cells, suggesting adaptations to support viral replication. Overall, these data suggest that SVV infection remodels the transcriptome of bystander and infected lung-resident T cells and macrophages.
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Pulmón , Macaca mulatta , Animales , Pulmón/inmunología , Pulmón/virología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/virología , Transcriptoma , Linfocitos T/inmunología , Varicellovirus/fisiología , Varicellovirus/inmunología , Macrófagos/inmunología , Macrófagos/virología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/fisiología , Modelos Animales de Enfermedad , Análisis de la Célula IndividualRESUMEN
Simian varicella virus (SVV) produces peripheral inflammatory responses during varicella (primary infection) and zoster (reactivation) in rhesus macaques (RM). However, it is unclear if peripheral measures are accurate proxies for central nervous system (CNS) responses. Thus, we analyzed cytokine and Aß42/Aß40 changes in paired serum and cerebrospinal fluid (CSF) during the course of infection. During varicella and zoster, every RM had variable changes in serum and CSF cytokine and Aß42/Aß40 levels compared to pre-inoculation levels. Overall, peripheral infection appears to affect CNS cytokine and Aß42/Aß40 levels independent of serum responses, suggesting that peripheral disease may contribute to CNS disease.
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Péptidos beta-Amiloides , Citocinas , Macaca mulatta , Animales , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/sangre , Citocinas/líquido cefalorraquídeo , Citocinas/sangre , Activación Viral , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/sangre , Varicellovirus/genética , Varicellovirus/inmunología , Herpesvirus Humano 3/patogenicidad , Herpesvirus Humano 3/inmunología , Infecciones por Herpesviridae/líquido cefalorraquídeo , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/sangre , Infecciones por Herpesviridae/inmunología , Masculino , Herpes Zóster/líquido cefalorraquídeo , Herpes Zóster/virología , Herpes Zóster/sangre , Herpes Zóster/inmunología , Enfermedades de los Monos/virología , Enfermedades de los Monos/líquido cefalorraquídeo , Enfermedades de los Monos/sangreRESUMEN
Feline herpesvirus type 1 (FHV-1) is endemic in captive cheetahs and sporadically causes devastating disease. Modified live vaccines (MLV), intended for use in domestic cats, are used in some captive cheetah populations and have been anecdotally linked to disease in certain subpopulations. Ten FHV-1 isolates from ten captive cheetahs and one isolate from an MLV used to inoculate four of the host animals were analyzed. Viral DNA was extracted for full-genome sequencing by Illumina MiSeq with viral genomes then used for phylogenomic and recombinational analyses. The FHV-1 shed by vaccinated cheetahs were almost identical to the MLV, with few variants among viral genomes. Eight cheetah FHV-1 isolates and the MLV were grouped in a clade along with FHV-1 isolates from domestic cats in the USA. The remaining two cheetah FHV-1 isolates (unknown host vaccine status) were not associated with a clade. The likely ancestral origin of these two isolates involves recombination events between Australian domestic cat and cheetah FHV-1 isolates. Collectively, these data suggest that the MLV is capable of causing clinical disease and viral shedding in some cheetahs and represents evidence of interspecies transmission of virus between domestic and wild cats.
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Acinonyx/virología , Enfermedades de los Gatos , Infecciones por Herpesviridae , Varicellovirus , Animales , Enfermedades de los Gatos/prevención & control , Enfermedades de los Gatos/virología , Gatos , Línea Celular , Genoma Viral , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/veterinaria , Vacunas Atenuadas/administración & dosificación , Varicellovirus/genética , Varicellovirus/inmunologíaRESUMEN
Herpesviruses are attractive vaccine vector candidates due to their large double stranded DNA genome and latency characteristics. Within the scope of veterinary vaccines, herpesvirus-vectored vaccines have been well studied and commercially available vectored vaccines are used to help prevent diseases in different animal species. Felid alphaherpesvirus 1 (FHV-1) has been characterised as a vector candidate to protect against a range of feline pathogens. In this review we highlight the methods used to construct FHV-1 based vaccines and their outcomes, while also proposing alternative uses for FHV-1 as a viral vector.
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Enfermedades de los Gatos/prevención & control , Vectores Genéticos/normas , Inmunización/veterinaria , Varicellovirus/inmunología , Animales , Enfermedades de los Gatos/inmunología , Enfermedades de los Gatos/virología , Gatos , Vectores Genéticos/genética , Vacunas Sintéticas/inmunología , Varicellovirus/genéticaRESUMEN
BACKGROUND: The feline viral rhinotracheitis, calicivirus, and panleukopenia (FVRCP) vaccine, prepared from viruses grown in the Crandell-Rees feline kidney cell line, can induce antibodies to cross-react with feline kidney tissues. OBJECTIVES: This study surveyed the prevalence of autoantibodies to feline kidney tissues and their association with the frequency of FVRCP vaccination. METHODS: Serum samples and kidneys were collected from 156 live and 26 cadaveric cats. Antibodies that bind to kidney tissues and antibodies to the FVRCP antigen were determined by enzyme-linked immunosorbent assay (ELISA), and kidney-bound antibody patterns were investigated by examining immunofluorescence. Proteins recognized by antibodies were identified by Western blot analysis. RESULTS: The prevalences of autoantibodies that bind to kidney tissues in cats were 41% and 13% by ELISA and immunofluorescence, respectively. Kidney-bound antibodies were observed at interstitial cells, apical border, and cytoplasm of proximal and distal tubules; the antibodies were bound to proteins with molecular weights of 40, 47, 38, and 20 kDa. There was no direct link between vaccination and anti-kidney antibodies, but positive antibodies to kidney tissues were significantly associated with the anti-FVRCP antibody. The odds ratio or association in finding the autoantibody in cats with the antibody to FVRCP was 2.8 times higher than that in cats without the antibody to FVRCP. CONCLUSIONS: These preliminary results demonstrate an association between anti-FVRCP and anti-cat kidney tissues. However, an increase in the risk of inducing kidney-bound antibodies by repeat vaccinations could not be shown directly. It will be interesting to expand the sample size and follow-up on whether these autoantibodies can lead to kidney function impairment.
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Anticuerpos Antivirales/análisis , Autoanticuerpos/análisis , Calicivirus Felino/inmunología , Enfermedades de los Gatos/prevención & control , Virus de la Panleucopenia Felina/inmunología , Varicellovirus/inmunología , Vacunas Virales/inmunología , Animales , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/veterinaria , Gatos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Panleucopenia Felina/prevención & control , Femenino , Técnica del Anticuerpo Fluorescente/veterinaria , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/veterinaria , Riñón/virología , Masculino , RiesgoRESUMEN
In order to analyse the prevalence of cat viral diseases in China, including feline parvovirus (FPV), feline calicivirus (FCV), feline herpesvirus 1 (FHV-1), feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV) and feline infectious peritonitis virus (FIPV), a total of 1,326 samples of cats from 16 cities were investigated from 2016 to 2019. Collectively, 1,060 (79.9%) cats were tested positive for at least one virus in nucleotide detection, and the positive rates of cat exposure to FeLV, FPV, FHV-1, FCV, FIV and FIPV were 59.6%, 19.2%, 16.3%, 14.2%, 1.5% and 0.5%, respectively. The prevalence of FHV-1 and FPV was dominant in winter and spring. Cats from north China showed a higher positive rate of viral infection than that of cats from south China. The virus infection is not highly correlated with age, except that FPV is prone to occur within the age of 12 months. In the serological survey, the seroprevalences of 267 vaccinated cats to FPV, FCV and FHV-1 were 83.9%, 58.3% and 44.0%, respectively. Meanwhile, the seroprevalences of 39 unvaccinated cats to FPV, FCV and FHV-1 were 76.9% (30/39), 82.4% (28/34) and 58.6% (17/29), respectively. This study demonstrated that a high prevalence of the six viral diseases in China and the insufficient serological potency of FCV and FHV-1 remind the urgency for more effective vaccines.
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Anticuerpos Antivirales/sangre , Enfermedades de los Gatos/virología , Virosis/veterinaria , Virus/aislamiento & purificación , Animales , Calicivirus Felino/inmunología , Calicivirus Felino/aislamiento & purificación , Enfermedades de los Gatos/epidemiología , Gatos , China/epidemiología , Enfermedades Transmisibles/veterinaria , Coronavirus Felino/inmunología , Coronavirus Felino/aislamiento & purificación , Virus de la Panleucopenia Felina/inmunología , Virus de la Panleucopenia Felina/aislamiento & purificación , Femenino , Virus de la Inmunodeficiencia Felina/inmunología , Virus de la Inmunodeficiencia Felina/aislamiento & purificación , Virus de la Leucemia Felina/inmunología , Virus de la Leucemia Felina/aislamiento & purificación , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Estudios Seroepidemiológicos , Varicellovirus/inmunología , Varicellovirus/aislamiento & purificación , Virosis/epidemiología , Virus/genética , Virus/inmunologíaRESUMEN
Chickenpox is caused by varicella-zoster-virus (VZV) and is highly contagious. Immigration detention settings are a high-risk environment for primary VZV transmission, with large, rapidly-changing populations in close quarters, and higher susceptibility among non-UK-born individuals. During outbreaks, operational challenges occur in detention settings because of high-turnover and the potential need to implement population movement restriction for prolonged periods. Between December 2017 and February 2018, four cases of chickenpox were notified amongst 799 detainees in an immigration removal centre (IRC). Microbiological investigations included case confirmation by vesicular fluid polymerase chain reaction, and VZV serology for susceptibility testing. Control measures involved movement restrictions, isolation of cases, quarantining and cohorting of non-immune contacts and extending VZV immunity testing to the wider detainee population to support outbreak management. Immunity was tested for 301/532 (57%) detainees, of whom 24 (8%) were non-immune. The level of non-immunity was lower than expected based on the existing literature on VZV seroprevalence in detained populations in England. Serology results identified non-immune contacts who could be cohorted and, due to the lack of isolation capacity, allowed the placement of cases with immune detainees. The widespread immunity testing of all detainees was proving challenging to sustain because it required significant resources and was having a severe impact on operational capacity and the ability to maintain core business activities at the IRC. Therefore, mathematical modelling was used to assess the impact of scaling back mass immunity testing. Modelling demonstrated that interrupting testing posed a risk of one additional case compared to continuing with testing. As such, the decision was made to stop testing, and the outbreak was successfully controlled without excessive strain on resources. Operational challenges generated learning for future outbreaks, with implications for a local and national policy on IRC staff occupational health requirements, and proposed reception screening of detainees for VZV immunity.
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Varicela/epidemiología , Brotes de Enfermedades , Transmisión de Enfermedad Infecciosa/prevención & control , Emigrantes e Inmigrantes , Modelos Teóricos , Pruebas Serológicas/métodos , Varicellovirus/inmunología , Adolescente , Adulto , Anciano , Varicela/prevención & control , Varicela/transmisión , Inglaterra/epidemiología , Métodos Epidemiológicos , Humanos , Masculino , Persona de Mediana Edad , Aislamiento de Pacientes , Reacción en Cadena de la Polimerasa , Cuarentena , Varicellovirus/aislamiento & purificación , Adulto JovenRESUMEN
OBJECTIVES: Vaccination against feline herpesvirus-1 (FHV-1) is recommended for all cats. However, it is unknown how adult healthy cats with different pre-vaccination antibodies respond to FHV-1 vaccination in the field. The aim of the study was to determine the prevalence of neutralising antibodies against FHV-1 in healthy adult cats and the response to FHV-1 vaccination within 28 days of vaccination. METHODS: One hundred and ten cats (⩾1 year of age) that had not received a vaccination within the past 12 months were vaccinated with a combined FHV-1 vaccine. Antibodies against FHV-1 were determined before vaccination (day 0), on day 7 and day 28 by serum neutralisation test. Uni- and multivariate statistical analyses were used to determine factors associated with the presence of pre-vaccination antibodies and response to vaccination. RESULTS: Pre-vaccination neutralising antibody titres (⩾10) were present in 40.9% of cats (45/110; 95% confidence interval [CI] 32.2-50.3); titres were generally low (range 10-640). Antibody response to vaccination (⩾four-fold titre increase) was observed in 8.3% (9/109; 95% CI 4.2-15.1). Cats ⩾2 years of age were more likely to have pre-vaccination neutralising antibodies than cats aged between 1 and 2 years (odds ratio [OR] 24.619; P = 0.005). Cats from breeders were more likely to have pre-vaccination neutralising antibodies than privately owned cats (OR 7.070; P = 0.007). Domestic shorthair cats were more likely to have an at least four-fold titre increase vs purebred cats (OR 11.22; P = 0.027). CONCLUSIONS AND RELEVANCE: Many cats have no detectable neutralising antibodies against FHV-1 despite previous vaccinations and fail to develop a ⩾four-fold titre increase after vaccination. This is likely because older cats and cats with a higher FHV-1 exposure risk are more likely to get infected with FHV-1 and thus to have FHV-1 neutralizing antibodies. Purebred cats more often fail to develop a ⩾four-fold titre increase after vaccination.
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Anticuerpos Antivirales/sangre , Enfermedades de los Gatos , Infecciones por Herpesviridae , Varicellovirus/inmunología , Vacunas Virales/inmunología , Animales , Enfermedades de los Gatos/inmunología , Enfermedades de los Gatos/prevención & control , Gatos , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/veterinaria , Vacunación/veterinariaRESUMEN
Caprine herpesvirus 1 (CpHV-1) infection is associated with clinical manifestations related to animal age, with high mortality in kids and infertility in adults. Given the scarcity of research about the epidemiological situation of this infection in Brazilian flocks, we aimed to conduct a cross-sectional descriptive study to detect antibodies against CpHV-1 in goats in the state of São Paulo, Brazil. Fifty-five male and female goats kids and adult were assessed in this study. Blood serum was analyzed by a commercial ELISA kit to detect antibodies against CpHV-1, which had not been used in Brazil before. No animals were reactive. Brazil lacks information about CpHV-1 infection in goat flocks. Continuing the study is crucial to understand the epidemiological situation of the disease and establish protocols for infection control.(AU)
A infecção pelo Herpesvírus Caprino tipo 1 (CpHv-1) está associada a manifestações clínicas relacionadas à idade dos animais, com alta mortalidade em filhotes e infertilidade em adultos. Diante da escassez de estudos sobre situação epidemiológica dessa infecção nos rebanhos brasileiros, a presente pesquisa teve como objetivo realizar um estudo transversal e descritivo para a detecção de anticorpos anti-Herpesvírus Caprino tipo 1 em caprinos do estado de São Paulo, Brasil. Foram avaliados 55 caprinos machos e fêmeas, filhotes e adultos. O soro sanguíneo foi analisado por um kit ELISA comercial para detecção de anticorpos contra CpHv-1, de utilização inédita no Brasil. Nenhum animal estudado foi sororreagente. O Brasil carece de informações acerca da infecção pelo Herpesvírus Caprino tipo 1 nos rebanhos caprinos do país. A continuidade do estudo é imprescindível para compreender a situação epidemiológica da enfermidade e estabelecer protocolos para controle da infecção.(AU)
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Animales , Masculino , Femenino , Péptidos/inmunología , Cabras/virología , Glicoproteínas/inmunología , Varicellovirus/inmunología , Infecciones por Herpesviridae/diagnóstico , Rumiantes/virología , Ensayo de Inmunoadsorción Enzimática/métodos , Estudios Transversales , Varicellovirus/aislamiento & purificación , Infecciones por Herpesviridae/inmunologíaRESUMEN
Caprine alphaherpesvirus 1 (CpHV-1) is a worldwide pathogen of goats and is closely related to Bovine alphaherpevirus 1 (BoHV-1). We herein studied the antigenic relationships of CpHV-1 with BoHV-1 and investigated the pathogenesis of CpHV-1 in kids and calves. Monoclonal antibody reactivity revealed that CpHV-1 and BoHV-1 share immunogenic epitopes in the major envelope glycoproteins gB, gC and gD. The antigenic relationship was further demonstrated by virus-neutralizing assays, in which CpHV-1 and BoHV-1 antisera presented varied degrees of cross-neutralization against the respective heterologous viruses. Although cross-neutralization was observed between both viruses and the heterologous antisera, BoHV-1 antisera neutralized CpHV-1 with higher efficiency than CpHV-1 antisera neutralized BoHV-1. Hence, the antigenic cross-reactivity between CpHV-1 and BoHV-1 should be considered upon serologic testing of goats and cattle in regions where the two viruses co-circulate. Intranasal (IN) inoculation of CpHV-1 (WI13-46 isolate) in seven seronegative kids resulted in efficient viral replication in the respiratory tract. Additionally, mild to moderate systemic and respiratory signs were observed, including apathy, hyperthermia, nasal discharge and respiratory distress. Dexamethasone administration to the inoculated kids between days 36 and 40 pi did not result in virus shedding in nasal secretions. However, latent infection had been established, as evidenced by the detection of CpHV-1 DNA in trigeminal ganglia and olfactory bulbs of kids euthanized at day 67 pi. Contrasting with the outcome of infection in kids, IN inoculation of CpHV-1 in calves did not result in productive infection as no virus replication or shedding were detected, and the animals did not develop clinical signs nor seroconverted. The animal experiments demonstrated that CpHV-1 was able to produce respiratory disease in kids, but did not replicate to detectable levels in calves.
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Antígenos Virales/inmunología , Enfermedades de los Bovinos/patología , Enfermedades de los Bovinos/virología , Enfermedades de las Cabras/patología , Enfermedades de las Cabras/virología , Infecciones por Herpesviridae/veterinaria , Varicellovirus/inmunología , Animales , Animales Recién Nacidos , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Bovinos , Reacciones Cruzadas , Epítopos/inmunología , Cabras , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/virología , Varicellovirus/clasificaciónRESUMEN
BACKGROUND: Feline herpesvirus-1 (FHV-1) infection can result in serious morbidity and mortality, especially in kittens. Immunotherapy using liposome-toll-like receptor (TLR) ligand complexes (LTC) has been shown to activate innate immune responses. OBJECTIVES: To determine in kittens whether mucosal administration of LTC before FHV-1 inoculation would decrease severity of clinical signs and decrease quantities of FHV-1 DNA in materials collected on oropharyngeal swabs. ANIMALS: Nineteen, 14-week-old, purpose-bred kittens. METHODS: Pilot clinical trial with 2 groups of kittens allocated to either an LTC or control group. The LTC were administered into both nares and the oropharynx of the 12 LTC group kittens, and all 19 kittens were inoculated with FHV-1 24 hours later. Clinical scores were determined daily for 28 days, and oropharyngeal mucosal materials were collected every 7 days to assess FHV-1 DNA quantities for comparison between groups. RESULTS: Conjunctivitis was more common in kittens in the control group on Days 15-28 (P = .01) and Days 1-28 (P = .02). Total respiratory scores were higher in the LTC group on days 15-28 (P = .03). The LTC group had significantly decreased FHV-1 DNA on swabs when compared to the control group on some postinoculation days, using 2 methods of calculation. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of LTC to kittens was shown to decrease FHV-1 DNA and some manifestations of illness in kittens when administrated 24 hours before inoculation, suggesting clinical benefit.
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Enfermedades de los Gatos/virología , Infecciones por Herpesviridae/veterinaria , Liposomas/administración & dosificación , Receptores Toll-Like/agonistas , Varicellovirus/inmunología , Animales , Enfermedades de los Gatos/inmunología , Enfermedades de los Gatos/prevención & control , Gatos , ADN Viral/aislamiento & purificación , Femenino , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/prevención & control , Inmunidad Innata , Masculino , Membrana Mucosa/inmunología , Membrana Mucosa/virología , Proyectos Piloto , Varicellovirus/aislamiento & purificaciónRESUMEN
This study tested for association between bovine viral diarrhoea virus (BVDv) and cervid herpesvirus type-1 (CvHV-1) exposure and abortion in New Zealand farmed red deer. Rising two-year-old (R2, n = 22,130) and mixed-age (MA, n = 36,223) hinds from 87 and 71 herds, respectively, throughout New Zealand were pregnancy tested using ultrasound early in gestation (Scan-1) and 55-89 days later (Scan-2) to detect mid-term abortion. Sera from aborted and non-aborted hinds at Scan-2 were tested for BVDv and CvHV-1 using virus neutralisation tests. Available uteri from aborted hinds and from hinds not rearing a calf to weaning were tested by PCR for herpesvirus DNA. In herds with aborted hinds, 10.3% of 639 R2 and 17.2% of 302 MA hinds were sero-positive for BVDv and 18.6% of 613 R2 and 68.5% of 232 MA hinds were sero-positive for CvHV-1. There was no association between BVDv sero-status and abortion at animal level (R2 p = 0.36, MA p = 0.76) whereas CvHV-1 sero-positivity was negatively associated with abortion in MA hinds (p = 0.01) but not in R2 hinds (p = 0.36), MA). Eleven of 108 uteri from aborted R2 hinds but no MA hinds were positive for herpesvirus DNA. Vaginal samples from four R2 and one MA aborted hinds tested were negative for herpesvirus DNA. A Cervid Rhadinovirus type-2 (CRhV-2) was identified in seven PCR positive uteri samples. Findings suggest that BVDv and CvHV-1 may not be associated with abortion in R2 hinds, but association needs to be tested further in MA hinds. The role of CRhV-2 requires clarification.
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Aborto Veterinario/virología , Diarrea Mucosa Bovina Viral/virología , Ciervos/virología , Virus de la Diarrea Viral Bovina/inmunología , Infecciones por Herpesviridae/veterinaria , Varicellovirus/inmunología , Aborto Veterinario/epidemiología , Animales , Diarrea Mucosa Bovina Viral/epidemiología , Bovinos , Granjas , Femenino , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/virología , Nueva Zelanda/epidemiología , Embarazo , DesteteRESUMEN
Caprine Herpesvirus type 1 (CpHV-1) is a species-specific herpes virus able to induce apoptosis in several biological systems. In the present study we aimed to investigate the ability of CpHV-1 to reduce cells viability, to replicate and to cause cell death also in human cancer cell lines. We tested the CpHV-1 effects on HEL-299, Vero, MDA-MB-468, HeLa, U2OS, PC3, A549 and K562 neoplastic cell lines and on MDBK cells. Firstly, we evaluated the effect of CpHV-1 infection on cell viability by MTT assay and our data showed that CpHV-1 can induce a marked cytopathic effect (CPE) in most of cell lines tested, except for HEL-299, Vero and K562 cells. The reduction of cell viability was associated with a significant increase of viral production. We next investigated if CpHV-1 was able to induce cell death and so through western blotting analysis we evaluated cleaved caspase 3, LC3II and p62 protein levels after infection. Caspase 3 activation was detected in MDBK cells and, even if at different times p.i., also in MDA-MB-468, U2OS, and PC3 cell lines, while LC3II increase and concomitant p62 protein reduction were observed only in U2OS, and A549 cells, no significant alteration of these proteins was observed in the other cell lines tested. Finally, to confirm virus ability to trigger apoptosis we performed an Annexin-V apoptosis test after 24 h p.i. Although we need to further explore mechanisms underlying CpHV-1 treatment, this study could serve as the basis for the development of new treatment options aiming to fight several cancer types.
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Neoplasias/terapia , Viroterapia Oncolítica/métodos , Virus Oncolíticos/inmunología , Varicellovirus/inmunología , Animales , Apoptosis/inmunología , Autofagia/inmunología , Bovinos , Línea Celular Tumoral , Supervivencia Celular/inmunología , Chlorocebus aethiops , Humanos , Neoplasias/inmunología , Pruebas de Toxicidad , Células VeroRESUMEN
Equid herpesviruses types 1 (EHV-1) and 9 (EHV-9) are unusual among herpesviruses in that they lack strong host specificity, and the full extent of their host range remains unclear. The virus establishes latency for long periods and can be reactivated and shed, resulting in clinical disease in susceptible species. A sensitive and specific peptide-based enzyme-linked immunosorbent assay was developed to study the seroprevalence of both viruses in a broad range of species among both wild and captive populations. We used this assay to study the seroprevalences of EHV-1 and EHV-9 in a natural population of the highly endangered Grévy's zebra ( Equus grevyi) in Kenya, sampled during a 4-yr period (2012-15). The results were compared with those obtained from captive Grévy's zebras from a previous study. The wild population had a significantly higher seroprevalence of EHV-9 compared with the captive population, suggesting that captivity might reduce exposure to this serotype. In contrast, the seroprevalences of EHV-1 between captive and wild groups was not significantly different. The seroprevalence of EHV-9 was not significantly higher than EHV-1 in zebras within the wild Kenyan population.
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Anticuerpos Antivirales/sangre , Equidae/sangre , Varicellovirus/inmunología , Animales , Animales Salvajes , Kenia/epidemiología , Estudios Seroepidemiológicos , Latencia del VirusRESUMEN
PURPOSE: Infection by Human Herpes Viruses (HHV) types 1-3, are prevalent throughout the world. It is known that radiotherapy can reactivate HHVs, but it is unclear how and to what extent reactivations can interact with or affect radiotherapeutic efficacy, patient outcomes and mortality risk. Herein, we aim to summarize what is known about Herpes Simplex Virus (HSV)-1,2 and Varicella Zoster Virus (VZV) pathophysiology as it relates to tumor biology, radiotherapy, chemo-radiotherapy, diagnosis and management so as to optimize cancer treatment in the setting of active HHV infection. Our secondary aim is to emphasize the need for further research to elucidate the potential adverse effects of active HHV infection in irradiated tumor tissue and to design optimal management strategies to incorporate into cancer management guidelines. MATERIALS AND METHODS: The literature regarding herpetic infection, herpetic reactivation, and recurrence occurring during radiotherapy and that regarding treatment guidelines for herpetic infections are reviewed. We aim to provide the oncologist with a reference for the infectious dangers of herpetic reactivation in patients under their care and well established methods for prevention, diagnosis, and treatment of such infections. Pain management is also considered. CONCLUSIONS: In the radiotherapeutic setting, serologic assays for HSV-1 and HSV-2 are feasible and can alert the clinician to patients at risk for viral reactivation. RT-PCR is specific in identifying the exact viral culprit and is the preferred diagnostic method to measure interventional efficacy. It can also differentiate between herpetic infection and radionecrosis. The MicroTrak® HSV1/HSV2/VZV staining kit has high sensitivity and specificity in acute lesions, is also the most rapid means to confirm diagnosis. Herpetic reactivation and recurrences during radiotherapy can cause interruptions, cessations, or prolongations of the radiotherapeutic course, thus decreasing the biologically effective dose, to sub-therapeutic levels. Active HHV infection within the treatment volume results in increased tumor radio-resistance and potentially sub-therapeutic care if left untreated. Visceral reactivations may result in fatality and therefore, a high index of suspicion is important to identify these active infections. The fact that such infections may be mistaken for acute and/or late radiation effects, leading to less than optimal treatment decisions, makes knowledge of this problem even more relevant. To minimize the risk of these sequelae, prompt anti-viral therapy is recommended, lasting the course of radiotherapy.
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Manejo de la Enfermedad , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/terapia , Neoplasias/complicaciones , Radioterapia/efectos adversos , Activación Viral/efectos de los fármacos , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 2/inmunología , Humanos , Técnicas de Diagnóstico Molecular , Neoplasias/terapia , Pruebas Serológicas , Varicellovirus/inmunologíaRESUMEN
Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure 'opportunities' through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed.
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Vacuna contra la Varicela/administración & dosificación , Vacuna contra la Varicela/inmunología , Herpes Zóster/epidemiología , Herpes Zóster/inmunología , Inmunidad Celular , Varicellovirus/inmunología , Activación Viral , Humanos , Modelos Biológicos , Modelos Estadísticos , Medición de Riesgo , Varicellovirus/fisiologíaRESUMEN
Varicella zoster virus (VZV) causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. Infection of rhesus macaques with simian varicella virus (SVV) recapitulates VZV pathogenesis in humans thus representing a suitable animal model for VZV infection. While the type I interferon (IFN) response has been shown to affect VZV replication, the virus employs counter mechanisms to prevent the induction of anti-viral IFN stimulated genes (ISG). Here, we demonstrate that SVV inhibits type I IFN-activated signal transduction via the JAK-STAT pathway. SVV-infected rhesus fibroblasts were refractory to IFN stimulation displaying reduced protein levels of IRF9 and lacking STAT2 phosphorylation. Since previous work implicated involvement of the VZV immediate early gene product ORF63 in preventing ISG-induction we studied the role of SVV ORF63 in generating resistance to IFN treatment. Interestingly, SVV ORF63 did not affect STAT2 phosphorylation but caused IRF9 degradation in a proteasome-dependent manner, suggesting that SVV employs multiple mechanisms to counteract the effect of IFN. Control of SVV ORF63 protein levels via fusion to a dihydrofolate reductase (DHFR)-degradation domain additionally confirmed its requirement for viral replication. Our results also show a prominent reduction of IRF9 and inhibition of STAT2 phosphorylation in VZV-infected cells. In addition, cells expressing VZV ORF63 blocked IFN-stimulation and displayed reduced levels of the IRF9 protein. Taken together, our data suggest that varicella ORF63 prevents ISG-induction both directly via IRF9 degradation and indirectly via transcriptional control of viral proteins that interfere with STAT2 phosphorylation. SVV and VZV thus encode multiple viral gene products that tightly control IFN-induced anti-viral responses.
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Infecciones por Herpesviridae/metabolismo , Interacciones Huésped-Patógeno , Interferón Tipo I/metabolismo , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Varicellovirus/fisiología , Animales , Línea Celular , Cercopithecinae , Varicela/inmunología , Varicela/metabolismo , Varicela/patología , Varicela/virología , ADN Recombinante/metabolismo , Regulación Viral de la Expresión Génica , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/virología , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/fisiología , Humanos , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Inmunidad Innata , Interferón Tipo I/antagonistas & inhibidores , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/antagonistas & inhibidores , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/genética , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/metabolismo , Fosforilación , Complejo de la Endopetidasa Proteasomal , Procesamiento Proteico-Postraduccional , Proteolisis , Proteínas Recombinantes/metabolismo , Factores de Transcripción STAT/genética , Varicellovirus/inmunologíaRESUMEN
Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation.
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Infecciones por Herpesviridae/virología , Primates , Varicellovirus/patogenicidad , Animales , Biopsia , Modelos Animales de Enfermedad , Genotipo , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/patología , Interacciones Huésped-Patógeno , Humanos , Patología Molecular/métodos , Valor Predictivo de las Pruebas , Varicellovirus/genética , Varicellovirus/inmunología , Virología/métodos , Virulencia , Activación Viral , Latencia del VirusRESUMEN
UNLABELLED: Varicella-zoster virus (VZV) is the etiological agent of varicella (chickenpox) and herpes zoster (shingles). Primary VZV infection is believed to occur via the inhalation of virus either in respiratory droplets or from shedding varicella lesions or by direct contact with infectious vesicular fluid. However, the ensuing immune response in the lungs remains incompletely understood. We have shown that intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, recapitulates the hallmarks of acute and latent VZV infection in humans. In this study, we performed an in-depth analysis of the host immune response to acute SVV infection in the lungs and peripheral blood. We report that acute SVV infection results in a robust innate immune response in the lungs, characterized by the production of inflammatory cytokines, chemokines, and growth factors as well as an increased frequency of plasmacytoid dendritic cells (DCs) that corresponded with alpha interferon (IFN-α) production and a rapid decrease in viral loads in the lungs. This is followed by T and B cell proliferation, antibody production, T cell differentiation, and cytokine production, which correlate with the complete cessation of viral replication. Although terminally differentiated CD8 T cells became the predominant T cell population in bronchoalveolar lavage cells, a higher percentage of CD4 T cells were SVV specific, which suggests a critical role for these cells in the resolution of primary SVV infection in the lungs. Given the homology between SVV and VZV, our data provide insight into the immune response to VZV within the lung. IMPORTANCE: Although primary VZV infection occurs primarily via the respiratory route, the host response in the lungs and its contribution to the cessation of viral replication and establishment of latency remain poorly understood. The difficulty in accessing lung tissue and washes from individuals infected with VZV has hampered efforts to address this knowledge gap. SVV infection of rhesus macaques is an important model of VZV infection of humans; therefore, we utilized this animal model to gain a comprehensive view of the kinetics of the immune response to SVV in the lung and its relationship to the resolution of acute infection in respiratory tissues. These data not only advance our understanding of host immunity to VZV, a critical step in developing new vaccines, but also provide additional insight into immunity to respiratory pathogens.
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Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/patología , Pulmón/inmunología , Pulmón/patología , Varicellovirus/inmunología , Animales , Citocinas/metabolismo , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Femenino , Infecciones por Herpesviridae/virología , Pulmón/virología , Macaca mulatta , Masculino , Linfocitos T/inmunología , Carga ViralRESUMEN
Water buffalo (Bubalus bubalis) are susceptible to bovine herpesvirus type 1 (BoHV-1) and a species-specific herpesvirus, bubaline herpesvirus type 1 (BuHV-1). In this study, an attenuated marker BoHV-1 based vaccine against BuHV-1 challenge was evaluated to determine whether it induces protection from viral replication. One group of water buffalo calves was immunized with an attenuated BoHV-1 marker vaccine. A second group was not vaccinated and used as the control. During the post-vaccination period, we monitored the humoral immune response. The efficacy of the vaccine was tested after intranasal challenge of the calves with a BuHV-1 strain. The experiment showed that after vaccination, BuHV-1 replication was significantly reduced by approximately three titer points compared to the controls. The control animals showed high levels of viral shedding and mild signs associated with BuHV-1 infection. Therefore, our study provides evidence for the existence of cross-protection between BoHV-1 and BuHV-1 in buffalo calves.