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1.
J Gen Virol ; 105(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38767608

RESUMO

Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1ß, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-ß (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this 'at-risk' immunophenotype.


Assuntos
Citocinas , Infecções por Herpesviridae , Herpesvirus Equídeo 1 , Doenças dos Cavalos , Animais , Cavalos , Herpesvirus Equídeo 1/imunologia , Feminino , Doenças dos Cavalos/virologia , Doenças dos Cavalos/imunologia , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Citocinas/sangue , Citocinas/imunologia , Anticorpos Antivirais/sangue , Eliminação de Partículas Virais , Viremia/imunologia , Viremia/veterinária , Imunoglobulina G/sangue
2.
BMC Res Notes ; 17(1): 130, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730439

RESUMO

OBJECTIVE: In this study, we sought to determine whether faecal shedding occurs among SARS-COV-2 positive Ghanaians, as reported elsewhere. Hence we assayed for SARS-COV-2 in the stools of 48 SARS-COV-2 confirmed patients at the Ho Municipal Hospital in Ghana. RESULTS: Of the 48 COVID-19 patients, 45 (93.8%) had positive tests for SARS-CoV-2 faecal shedding. About 60% reported no respiratory symptoms, while only 2% (1 patient) reported gastrointestinal (GI) symptoms in the form of nausea. Other symptoms reported included headache (57.9%), weakness (57.9%), cough (52.6%), blocked/runny nose (47.4%), fever (31.6%), sore throat (31.6%), and shortness of breath (21.1%). One person complained of nausea (5.3%) Semi-quantitative comparison of the SARS COV-2 viral loads in matched respiratory and faecal samples using the cycle threshold (CT) values revealed no statistical differences. Furthermore, the duration between collection of respiratory and faecal samples did not have any direct influence on the differences in the CT values. This suggests that treatment and use of sewage for environmental surveillance of SARS COV-2 could be a potential public health countermeasure.


Assuntos
COVID-19 , Fezes , SARS-CoV-2 , Eliminação de Partículas Virais , Humanos , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/diagnóstico , Gana/epidemiologia , Fezes/virologia , Masculino , Feminino , SARS-CoV-2/isolamento & purificação , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Carga Viral , Infecções Assintomáticas/epidemiologia , Adolescente , Gastroenteropatias/virologia , Gastroenteropatias/epidemiologia , Gastroenteropatias/diagnóstico
3.
PLoS Pathog ; 20(5): e1011961, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701091

RESUMO

Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes at the 3' position of the NS4 gene and used this pool as our viral inoculum for in vivo infections of different mouse lines. We found that over the course of persistent CR6 infection, shed virus was predominantly colon-derived, and viral barcode richness decreased over time irrespective of host immune status, suggesting that persistent infection involves a series of reinfection events. In mice lacking the IFN-λ receptor, intestinal barcode richness was enhanced, correlating with increased viral intestinal replication. IL-4 treatment, which increases tuft cell numbers, also increased barcode richness, indicating the abundance of permissive tuft cells to be a bottleneck during CR6 infection. In mice lacking type I IFN signaling (Ifnar1-/-) or all IFN signaling (Stat1-/-), barcode diversity at extraintestinal sites was dramatically increased, implicating different IFNs as critical bottlenecks at specific tissue sites. Of interest, extraintestinal barcodes were overlapping but distinct from intestinal barcodes, indicating that disseminated virus represents a distinct viral population than that replicating in the intestine. Barcoded viruses are a valuable tool to explore the influence of host factors on viral diversity in the context of establishment and maintenance of infection as well as dissemination and have provided important insights into how NoV infection proceeds in immunocompetent and immunocompromised hosts.


Assuntos
Infecções por Caliciviridae , Interferons , Norovirus , Animais , Norovirus/fisiologia , Infecções por Caliciviridae/virologia , Infecções por Caliciviridae/imunologia , Camundongos , Interferons/metabolismo , Infecção Persistente/virologia , Infecção Persistente/imunologia , Camundongos Endogâmicos C57BL , Mucosa Intestinal/virologia , Mucosa Intestinal/imunologia , Gastroenterite/virologia , Replicação Viral , Camundongos Knockout , Imunidade Inata , Eliminação de Partículas Virais
4.
Artigo em Inglês | MEDLINE | ID: mdl-38747849

RESUMO

This study aimed to provide further insight into the evolutionary dynamics of SARS-CoV-2 by analyzing the case of a 40-year-old man who had previously undergone autologous hematopoietic stem cell transplantation due to a diffuse large B-cell lymphoma. He developed a persistent SARS-CoV-2 infection lasting at least 218 days and did not manifest a humoral immune response to the virus during this follow-up period. Whole-genome sequencing and viral cultures confirmed a persistent infection with a replication-positive virus that had undergone genetic variation for at least 196 days after symptom onset.


Assuntos
COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Eliminação de Partículas Virais , Humanos , Adulto , Masculino , COVID-19/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Linfoma Difuso de Grandes Células B/virologia , Linfoma Difuso de Grandes Células B/imunologia , Transplante de Células-Tronco Hematopoéticas , Sequenciamento Completo do Genoma
5.
Sci Rep ; 14(1): 11171, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750049

RESUMO

White-tailed deer (Odocoileus virginianus) have emerged as a reservoir host for SARS-CoV-2 given their susceptibility to infection and demonstrated high rates of seroprevalence and infection across the United States. As SARS-CoV-2 circulates within free-ranging white-tailed deer populations, there is the risk of transmission to other wildlife species and even back to the human population. The goal of this study was to determine the susceptibility, shedding, and immune response of North American elk (Cervus elaphus canadensis) to experimental infection with SARS-CoV-2, to determine if another wide-ranging cervid species could potentially serve as a reservoir host for the virus. Here we demonstrate that while North American elk do not develop clinical signs of disease, they do develop a neutralizing antibody response to infection, suggesting the virus is capable of replicating in this mammalian host. Additionally, we demonstrate SARS-CoV-2 RNA presence in the medial retropharyngeal lymph nodes of infected elk three weeks after experimental infection. Consistent with previous observations in humans, these data may highlight a mechanism of viral persistence for SARS-CoV-2 in elk.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , Cervos , RNA Viral , SARS-CoV-2 , Animais , Cervos/virologia , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , COVID-19/virologia , RNA Viral/genética , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Eliminação de Partículas Virais , Reservatórios de Doenças/virologia , Feminino
6.
Sci Adv ; 10(19): eadk9137, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728395

RESUMO

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesity's impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.


Assuntos
Modelos Animais de Doenças , Furões , Obesidade , Infecções por Orthomyxoviridae , Animais , Obesidade/virologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Pulmão/virologia , Pulmão/patologia , Índice de Gravidade de Doença , Dieta , Humanos , Eliminação de Partículas Virais , Influenza Humana/transmissão , Influenza Humana/virologia
7.
Nat Commun ; 15(1): 4018, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740820

RESUMO

Anti-HSV therapies are only suppressive because they do not eliminate latent HSV present in ganglionic neurons, the source of recurrent disease. We have developed a potentially curative approach against HSV infection, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Gene editing performed with two anti-HSV-1 meganucleases delivered by a combination of AAV9, AAV-Dj/8, and AAV-Rh10 can eliminate 90% or more of latent HSV DNA in mouse models of orofacial infection, and up to 97% of latent HSV DNA in mouse models of genital infection. Using a pharmacological approach to reactivate latent HSV-1, we demonstrate that ganglionic viral load reduction leads to a significant decrease of viral shedding in treated female mice. While therapy is well tolerated, in some instances, we observe hepatotoxicity at high doses and subtle histological evidence of neuronal injury without observable neurological signs or deficits. Simplification of the regimen through use of a single serotype (AAV9) delivering single meganuclease targeting a duplicated region of the HSV genome, dose reduction, and use of a neuron-specific promoter each results in improved tolerability while retaining efficacy. These results reinforce the curative potential of gene editing for HSV disease.


Assuntos
Dependovirus , Edição de Genes , Herpes Simples , Herpesvirus Humano 1 , Carga Viral , Eliminação de Partículas Virais , Animais , Edição de Genes/métodos , Feminino , Dependovirus/genética , Camundongos , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/fisiologia , Herpes Simples/genética , Herpes Simples/virologia , Herpes Simples/terapia , Modelos Animais de Doenças , Latência Viral/genética , Humanos , Vetores Genéticos/genética , Células Vero , Terapia Genética/métodos , Herpes Genital/terapia , Herpes Genital/virologia , DNA Viral/genética
8.
Elife ; 132024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38622989

RESUMO

Paxlovid, a SARS-CoV-2 antiviral, not only prevents severe illness but also curtails viral shedding, lowering transmission risks from treated patients. By fitting a mathematical model of within-host Omicron viral dynamics to electronic health records data from 208 hospitalized patients in Hong Kong, we estimate that Paxlovid can inhibit over 90% of viral replication. However, its effectiveness critically depends on the timing of treatment. If treatment is initiated three days after symptoms first appear, we estimate a 17% chance of a post-treatment viral rebound and a 12% (95% CI: 0-16%) reduction in overall infectiousness for non-rebound cases. Earlier treatment significantly elevates the risk of rebound without further reducing infectiousness, whereas starting beyond five days reduces its efficacy in curbing peak viral shedding. Among the 104 patients who received Paxlovid, 62% began treatment within an optimal three-to-five-day day window after symptoms appeared. Our findings indicate that broader global access to Paxlovid, coupled with appropriately timed treatment, can mitigate the severity and transmission of SARS-Cov-2.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Estudos Retrospectivos , Antivirais/uso terapêutico , SARS-CoV-2/fisiologia , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/virologia , Masculino , Hong Kong/epidemiologia , Feminino , Pessoa de Meia-Idade , Hospitalização , Eliminação de Partículas Virais , Idoso , Adulto , Resultado do Tratamento , Fatores de Tempo , Combinação de Medicamentos
9.
Nat Microbiol ; 9(5): 1231-1243, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649413

RESUMO

The 2022 mpox virus (MPXV) outbreak was sustained by human-to-human transmission; however, it is currently unclear which factors lead to sustained transmission of MPXV. Here we present Mastomys natalensis as a model for MPXV transmission after intraperitoneal, rectal, vaginal, aerosol and transdermal inoculation with an early 2022 human outbreak isolate (Clade IIb). Virus shedding and tissue replication were route dependent and occurred in the presence of self-resolving localized skin, lung, reproductive tract or rectal lesions. Mucosal inoculation via the rectal, vaginal and aerosol routes led to increased shedding, replication and a pro-inflammatory T cell profile compared with skin inoculation. Contact transmission was higher from rectally inoculated animals. This suggests that transmission might be sustained by increased susceptibility of the anal and genital mucosae for infection and subsequent virus release.


Assuntos
Mucosa , Infecções por Poxviridae , Eliminação de Partículas Virais , Animais , Feminino , Mucosa/virologia , Infecções por Poxviridae/transmissão , Infecções por Poxviridae/virologia , Infecções por Poxviridae/veterinária , Humanos , Replicação Viral , Modelos Animais de Doenças , Roedores/virologia , Masculino , Ratos , Vagina/virologia , Surtos de Doenças
10.
Vaccine ; 42(15): 3410-3419, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38641498

RESUMO

The application of recombinant herpesvirus of turkey, expressing the H9 hemagglutinin gene from low pathogenic avian influenza virus (LPAIV) H9N2 and the avian orthoavulavirus-1 (AOAV-1) (commonly known as Newcastle Disease virus (NDV)) fusion protein (F) as an rHVT-H9-F vaccine, is an alternative to currently used classical vaccines. This study investigated H9- and ND-specific humoral and mucosal responses, H9-specific cell-mediated immunity, and protection conferred by the rHVT-H9-F vaccine in specific pathogen-free (SPF) chickens. Vaccination elicited systemic NDV F- and AIV H9-specific antibody response but also local antibodies in eye wash fluid and oropharyngeal swabs. The ex vivo H9-specific stimulation of splenic and pulmonary T cells in the vaccinated group demonstrated the ability of vaccination to induce systemic and local cellular responses. The clinical protection against a challenge using a LPAIV H9N2 strain of the G1 lineage isolated in Morocco in 2016 was associated with a shorter duration of shedding along with reduced viral genome load in the upper respiratory tract and reduced cloacal shedding compared to unvaccinated controls.


Assuntos
Anticorpos Antivirais , Galinhas , Vírus da Influenza A Subtipo H9N2 , Vacinas contra Influenza , Influenza Aviária , Eliminação de Partículas Virais , Animais , Vírus da Influenza A Subtipo H9N2/imunologia , Vírus da Influenza A Subtipo H9N2/genética , Galinhas/imunologia , Influenza Aviária/prevenção & controle , Influenza Aviária/imunologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Eliminação de Partículas Virais/imunologia , Organismos Livres de Patógenos Específicos , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/genética , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Imunidade Celular , Herpesvirus Meleagrídeo 1/imunologia , Herpesvirus Meleagrídeo 1/genética , Vacinação/métodos , Imunidade Humoral , Vetores Genéticos/imunologia , Imunogenicidade da Vacina , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética
11.
MMWR Morb Mortal Wkly Rep ; 73(16): 365-371, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38668391

RESUMO

As population immunity to SARS-CoV-2 evolves and new variants emerge, the role and accuracy of antigen tests remain active questions. To describe recent test performance, the detection of SARS-CoV-2 by antigen testing was compared with that by reverse transcription-polymerase chain reaction (RT-PCR) and viral culture testing during November 2022-May 2023. Participants who were enrolled in a household transmission study completed daily symptom diaries and collected two nasal swabs (tested for SARS-CoV-2 via RT-PCR, culture, and antigen tests) each day for 10 days after enrollment. Among participants with SARS-CoV-2 infection, the percentages of positive antigen, RT-PCR, and culture results were calculated each day from the onset of symptoms or, in asymptomatic persons, from the date of the first positive test result. Antigen test sensitivity was calculated using RT-PCR and viral culture as references. The peak percentage of positive antigen (59.0%) and RT-PCR (83.0%) results occurred 3 days after onset, and the peak percentage of positive culture results (52%) occurred 2 days after onset. The sensitivity of antigen tests was 47% (95% CI = 44%-50%) and 80% (95% CI = 76%-85%) using RT-PCR and culture, respectively, as references. Clinicians should be aware of the lower sensitivity of antigen testing compared with RT-PCR, which might lead to false-negative results. This finding has implications for timely initiation of SARS-CoV-2 antiviral treatment, when early diagnosis is essential; clinicians should consider RT-PCR for persons for whom antiviral treatment is recommended. Persons in the community who are at high risk for severe COVID-19 illness and eligible for antiviral treatment should seek testing from health care providers with the goal of obtaining a more sensitive diagnostic test than antigen tests (i.e., an RT-PCR test).


Assuntos
Antígenos Virais , Teste Sorológico para COVID-19 , COVID-19 , SARS-CoV-2 , Eliminação de Partículas Virais , Humanos , COVID-19/diagnóstico , COVID-19/transmissão , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Adulto , Antígenos Virais/análise , Masculino , Sensibilidade e Especificidade , Feminino , Pessoa de Meia-Idade , Teste de Ácido Nucleico para COVID-19 , Adulto Jovem , Adolescente , Estados Unidos/epidemiologia , Idoso , Teste para COVID-19
12.
JCI Insight ; 9(9)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573774

RESUMO

The viral kinetics of documented SARS-CoV-2 infections exhibit a high degree of interindividual variability. We identified 6 distinct viral shedding patterns, which differed according to peak viral load, duration, expansion rate, and clearance rate, by clustering data from 768 infections in the National Basketball Association cohort. Omicron variant infections in previously vaccinated individuals generally led to lower cumulative shedding levels of SARS-CoV-2 than other scenarios. We then developed a mechanistic mathematical model that recapitulated 1,510 observed viral trajectories, including viral rebound and cases of reinfection. Lower peak viral loads were explained by a more rapid and sustained transition of susceptible cells to a refractory state during infection as well as by an earlier and more potent late, cytolytic immune response. Our results suggest that viral elimination occurs more rapidly during Omicron infection, following vaccination, and following reinfection due to enhanced innate and acquired immune responses. Because viral load has been linked with COVID-19 severity and transmission risk, our model provides a framework for understanding the wide range of observed SARS-CoV-2 infection outcomes.


Assuntos
COVID-19 , SARS-CoV-2 , Carga Viral , Eliminação de Partículas Virais , COVID-19/imunologia , COVID-19/virologia , Humanos , SARS-CoV-2/imunologia , Eliminação de Partículas Virais/imunologia , Cinética , Masculino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Reinfecção/imunologia , Reinfecção/virologia , Adulto , Feminino , Modelos Teóricos
13.
Emerg Microbes Infect ; 13(1): 2348526, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38683015

RESUMO

The foot-and-mouth disease virus (FMDV) Leader proteinase Lpro inhibits host mRNA translation and blocks the interferon response which promotes viral survival. Lpro is not required for viral replication in vitro but serotype A FMDV lacking Lpro has been shown to be attenuated in cattle and pigs. However, it is not known, whether leaderless viruses can cause persistent infection in vivo after simulated natural infection and whether the attenuated phenotype is the same in other serotypes. We have generated an FMDV O/FRA/1/2001 variant lacking most of the Lpro coding region (ΔLb). Cattle were inoculated intranasopharyngeally and observed for 35 days to determine if O FRA/1/2001 ΔLb is attenuated during the acute phase of infection and whether it can maintain a persistent infection in the upper respiratory tract. We found that although this leaderless virus can replicate in vitro in different cell lines, it is unable to establish an acute infection with vesicular lesions and viral shedding nor is it able to persistently infect bovine pharyngeal tissues.


Assuntos
Doenças dos Bovinos , Vírus da Febre Aftosa , Febre Aftosa , Infecção Persistente , Sorogrupo , Replicação Viral , Animais , Bovinos , Vírus da Febre Aftosa/genética , Vírus da Febre Aftosa/fisiologia , Vírus da Febre Aftosa/classificação , Vírus da Febre Aftosa/patogenicidade , Vírus da Febre Aftosa/isolamento & purificação , Febre Aftosa/virologia , Doenças dos Bovinos/virologia , Infecção Persistente/virologia , Linhagem Celular , Endopeptidases/genética , Endopeptidases/metabolismo , Eliminação de Partículas Virais
14.
Vet Immunol Immunopathol ; 271: 110753, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608406

RESUMO

Porcine epidemic diarrhea virus (PEDV) causes immensely large economic losses worldwide in the swine industry. PEDV attacks the intestine, disrupts intestinal epithelium morphology and barrier integrity, and results in profound diarrhea and high mortality. A commercially available isotonic protein solution (IPS) (Tonisity Px) has anecdotally been reported to be effective in supportive treatment of piglets with active PEDV infections. This study evaluated the effects of supplementing (or not) the drinking water of 14 day old PEDV-infected piglets with the IPS on the content of E-cadherin, fibronectin, interferon-alpha (IFN-α), and matrix metalloproteinase 9 (MMP-9) in duodenal tissue. The content of PEDV DNA in feces was also measured. Though both groups had similar PEDV shedding at day 1, IPS piglets had significantly lower PEDV shedding at day 5, 14 and 21. The IPS group also had a shorter duration of PEDV virus shedding. Levels of E-cadherin and fibronectin, both of which are structural proteins in the intestine, remained unchanged from baseline in the IPS group, whereas the same molecules decreased significantly in the control group. IFN-α, an antiviral cytokine, and MMP-9, an enzyme that aids in tissue remodeling, were increased at days 5 and 14 post infection, and then decreased at day 21 post-infection in the IPS group compared to control. Overall, the IPS used in this study enhanced epithelial intercellular adhesion (E-cadherin) and extracellular matrix structure (fibronectin), resulted in significantand favorable changes in MMP-9 activity, and favorably modulated IFN-α production. This is the first report of this panel of biomarkers, especially MMP-9 and IFN-α, in the face of in vivo PEDV infection. This is also the first report to investigate a commercially available swine product that does not need to be administered in solid feed, and that is already registered for use throughout Asia, Europe, South America, and North America. Overall, the results of this study serve to clarify the behavior of 4 key biomarkers in the presence of in vivo PEDV infection. The results also indicate that IPS (Tonisity Px) supplementation is a viable intervention to modulate the porcine intestinal immune response with favorable effects on the intestine.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Eliminação de Partículas Virais , Animais , Suínos , Vírus da Diarreia Epidêmica Suína/fisiologia , Vírus da Diarreia Epidêmica Suína/imunologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Doenças dos Suínos/virologia , Doenças dos Suínos/imunologia , Fibronectinas/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Caderinas/metabolismo , Intestinos/imunologia , Intestinos/virologia , Interferon-alfa/imunologia , Adesão Celular , Mucosa Intestinal/imunologia
15.
Viruses ; 16(4)2024 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-38675912

RESUMO

In this paper, we report the characterization of a genetically modified live-attenuated African swine fever virus (ASFV) field strain isolated from Vietnam. The isolate, ASFV-GUS-Vietnam, belongs to p72 genotype II, has six multi-gene family (MGF) genes deleted, and an Escherichia coli GusA gene (GUS) inserted. When six 6-8-week-old pigs were inoculated with ASFV-GUS-Vietnam oro-nasally (2 × 105 TCID50/pig), they developed viremia, mild fever, lethargy, and inappetence, and shed the virus in their oral and nasal secretions and feces. One of the pigs developed severe clinical signs and was euthanized 12 days post-infection, while the remaining five pigs recovered. When ASFV-GUS-Vietnam was inoculated intramuscularly (2 × 103 TCID50/pig) into four 6-8 weeks old pigs, they also developed viremia, mild fever, lethargy, inappetence, and shed the virus in their oral and nasal secretions and feces. Two contact pigs housed together with the four intramuscularly inoculated pigs, started to develop fever, viremia, loss of appetite, and lethargy 12 days post-contact, confirming horizontal transmission of ASFV-GUS-Vietnam. One of the contact pigs died of ASF on day 23 post-contact, while the other one recovered. The pigs that survived the exposure to ASFV-GUS-Vietnam via the mucosal or parenteral route were fully protected against the highly virulent ASFV Georgia 2007/1 challenge. This study showed that ASFV-GUS-Vietnam field isolate is able to induce complete protection in the majority of the pigs against highly virulent homologous ASFV challenge, but has the potential for horizontal transmission, and can be fatal in some animals. This study highlights the need for proper monitoring and surveillance when ASFV live-attenuated virus-based vaccines are used in the field for ASF control in endemic countries.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Animais , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/isolamento & purificação , Vírus da Febre Suína Africana/patogenicidade , Vírus da Febre Suína Africana/classificação , Febre Suína Africana/virologia , Suínos , Vietnã , Viremia , Genoma Viral , Genótipo , Deleção de Sequência , Eliminação de Partículas Virais , Filogenia
16.
Open Vet J ; 14(2): 617-629, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38549580

RESUMO

Background: Fowl adenovirus (FAdV) 8b causes huge economic losses in the poultry industry worldwide. Attenuated FAdV 8b could be useful in preventing FAdV infections globally and scale-up obstacles could be solved by bioreactor technology. Aim: This study was carried out to attenuate the FAdV 8b isolate, propagate it in a bioreactor, molecularly characterize the passage isolates, and determine the immunogenicity, efficacy, and shedding of the virus of chickens. Methods: FAdV serotype 8b (UPM11142) isolate was passaged on chicken embryo liver (CEL) cells until attenuation and propagated in a bioreactor (UPM11142P20B1). Hexon and fiber genes of the isolates were sequenced and analyzed. UPM11142P20B1 was administered to 116-day-old broiler chickens divided into four groups, A (control), B (non-booster), C (booster with UPM11142P20B1), and D (booster with inactivated UPM11142P5B1). Eight chickens from each group were challenged. Body weight (BW) and liver weight (LW), liver: BW ratio (LBR), FAdV antibody titer, T lymphocyte sub-populations in the liver, spleen and thymus; and challenge virus load in the liver and shedding in cloaca were measured at weekly intervals. Results: The isolate caused typical cytopathic effects on CEL cells typical of FAdV. Novel molecular changes in the genes occurred which could be markers for FAdV 8b attenuation. BW, LW, and LBR were similar among groups throughout the trial but the uninoculated control-challenged group (UCC) had significantly higher LBR than the inoculated and challenged groups at 35 dpi. Non-booster group had higher FAdV antibodies at all time points than the uninoculated control group (UCG); and the challenged booster groups had higher titer at 35 dpi than UCC. T lymphocytes increased at different time-points in the liver of inoculated chickens, and in the spleen and thymus as well, and was higher in the organs of inoculated challenged groups than the UCC. There was a significantly higher challenge virus load in the liver and cloaca of UCC chickens than in the non-booster chickens. Conclusion: UPM11142P20B1 was safe, efficacious, significantly reduced shedding, and is recommended as a candidate vaccine in the prevention and control of FAdV 8b infections in broiler chickens.


Assuntos
Infecções por Adenoviridae , Aviadenovirus , Doenças das Aves Domésticas , Embrião de Galinha , Animais , Galinhas , Sorogrupo , Eliminação de Partículas Virais , Infecções por Adenoviridae/prevenção & controle , Infecções por Adenoviridae/veterinária , Aviadenovirus/genética
17.
mBio ; 15(5): e0006424, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38546212

RESUMO

Mucosal immunity is important in protecting from upper respiratory tract influenza infection. Human challenge provides a unique model to define correlates of protection with baseline immune responses being correlated to the quantity and length of viral shedding and clinical outcomes. Here, we discuss recent work on mucosal and systemic correlates of protection (R. Bean, L. T. Giurgea, A. Han, L. Czajkowski, et al., mBio 15:e02372-23, 2024, https://doi.org/10.1128/mbio.02372-23) and place it in the context of previous work on mucosal immunity. We also discuss the importance of standardized assays to allow global comparison of relevant immune responses in defining correlates of protection. Correlates of protection are important for designing next-generation broadly protective influenza vaccines.


Assuntos
Imunidade nas Mucosas , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Humanos , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Influenza Humana/virologia , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Vírus da Influenza A Subtipo H1N1/imunologia , Eliminação de Partículas Virais , Animais
18.
Travel Med Infect Dis ; 59: 102698, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556220

RESUMO

BACKGROUND: Mpox virus (MPXV) has recently spread outside of sub-Saharan Africa. This large multicentre study was conducted in Lombardy, the most densely populated Italian region accounting for more than 40% of Italian cases. The present study aims to: i) evaluate the presence and the shedding duration of MPXV DNA in different body compartments correlating the MPXV viability with the time to onset of symptoms; ii) provide evidence of MPXV persistence in different body compartment as a source of infection and iii) characterize the MPXV evolution by whole genome sequencing (WGS) during the outbreak occurred in Italy. MATERIAL AND METHODS: The study included 353 patients with a laboratory-confirmed diagnosis of MPXV infection screened in several clinical specimens in the period May 24th - September 1st, 2022. Viral isolation was attempted from different biological matrices and complete genome sequencing was performed for 61 MPXV strains. RESULTS: MPXV DNA detection was more frequent in the skin (94.4%) with the longest median time of viral clearance (16 days). The actively-replicating virus in cell culture was obtained for 123/377 (32.6%) samples with a significant higher viral quantity on isolation positive samples (20 vs 31, p < 0.001). The phylogenetic analysis highlighted the high genetic identity of the MPXV strains collected, both globally and within the Lombardy region. CONCLUSION: Skin lesion is gold standard material and the high viral load and the actively-replicating virus observed in genital sites confirms that sexual contact plays a key role in the viral transmission.


Assuntos
DNA Viral , Surtos de Doenças , Eliminação de Partículas Virais , Humanos , Itália/epidemiologia , DNA Viral/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Filogenia , Adulto Jovem , Infecções por Picornaviridae/epidemiologia , Infecções por Picornaviridae/virologia , Adolescente , Sequenciamento Completo do Genoma , Idoso , Criança
19.
Am J Vet Res ; 85(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38457927

RESUMO

OBJECTIVE: Compare immune responses induced by 2 commercial intranasal (IN) modified-live viral (MLV) vaccines given individually or coadministered and evaluate prevention of infection and lung pathology following bovine herpesvirus-1 (BHV-1) challenge. ANIMALS: 36 male Holstein calves (ages, 5 to 12 days). METHODS: In a randomized complete block design, each calf received an IN injection of either vaccine diluent (Placebo), an MLV vaccine containing bovine herpesvirus-1 (BHV-1; N3), bovine coronavirus vaccine (BC), or both N3 and BC (BC + N3) with a booster 4 weeks later. Nasal secretions and blood were collected weekly. Three weeks after the booster, the calves were challenged with BHV-1, sampled for virus shedding, and euthanized 10 days later to quantify lung pathology. The study period was September 7, 2020, to April 6, 2021. RESULTS: Calves were seropositive for BHV-1 and BC before vaccination. No significant difference in BC-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the BC versus BC + N3 group or BHV-1-specific serum immunoglobin G and nasal immunoglobin A antibody responses in the N3 versus BC + N3 group. Cytokine responses to BHV-1 and BC did not differ among groups. BHV-1 shedding after challenge was significantly reduced in N3 groups versus Placebo and BC. There was a significant reduction in lung pathology in the N3 + BC group versus Placebo. CLINICAL RELEVANCE: This study provides evidence an MLV vaccine containing BHV-1 and an MLV BC vaccine can be coadministered to neonatal calves without significantly altering immune responses to the 2 viruses or compromising the prevention of BHV-1 respiratory disease. Calves receiving the BC + N3 vaccine had a significant reduction in lung pathology after BHV-1 aerosol challenge.


Assuntos
Administração Intranasal , Animais Recém-Nascidos , Doenças dos Bovinos , Infecções por Coronavirus , Coronavirus Bovino , Infecções por Herpesviridae , Herpesvirus Bovino 1 , Vacinas Atenuadas , Vacinas Virais , Animais , Bovinos , Herpesvirus Bovino 1/imunologia , Administração Intranasal/veterinária , Masculino , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Coronavirus Bovino/imunologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Doenças dos Bovinos/imunologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Rinotraqueíte Infecciosa Bovina/imunologia , Eliminação de Partículas Virais , Anticorpos Antivirais/sangue , Distribuição Aleatória
20.
Gene Ther ; 31(5-6): 345-351, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467879

RESUMO

Adeno-associated viruses (AAV) are commonly used in the scientific field due to their diverse application range. However, AAV shedding, the release of virions from the host organism, can impact the safety of AAV-based approaches. An increasing number of authorities require the characterization of vector shedding in clinical trials. Recently, shedding of transduced laboratory animals has also gained attention regarding the necessary disposal measures of their waste products. However, no explicit international regulations for AAV-shedding waste exist. Generating insights into shedding dynamics becomes increasingly relevant to help authorities develop adequate regulations. To date, knowledge of AAV vector shedding in mice is very limited. Moreover, confirmation of functional shed AAV particles in mice is missing. Therefore, we examined feces, urine, and saliva of mice after CNS injection with AAV2/8. It revealed the presence of viral DNA fragments via qPCR for up to 4 days after injection. To examine AAV functionality we performed nested PCR and could not detect full-length viral genomes in any but two collected feces samples. Furthermore, a functional infection assay did not reveal evidence of intact AAV particles. Our findings are supposed to contribute murine shedding data as a foundation to help establish still lacking adequate biosafety regulations in the context of AAV shedding.


Assuntos
DNA Viral , Dependovirus , Vetores Genéticos , Eliminação de Partículas Virais , Animais , Dependovirus/genética , Camundongos , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , DNA Viral/genética , Fezes/virologia , Camundongos Endogâmicos C57BL , Saliva/virologia , Humanos
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