RESUMO
Despite significant improvements in vaccines and chemotherapeutic drugs, pathogenic RNA viruses continue to have a profound impact on the global economy and pose a serious threat to animal and human health through emerging and re-emerging outbreaks of diseases. To overcome the challenge of viral adaptation and evolution, increased vigilance is required. Particularly, antiviral drugs derived from new, natural sources provide an attractive strategy for controlling problematic viral diseases. In this antiviral study, we discovered a previously unknown bacterium, Mameliella sp. M20D2D8, by conducting an antiviral screening of marine microorganisms. An extract from M20D2D8 exhibited antiviral activity with low cytotoxicity and was found to be effective in vitro against multiple influenza virus strains: A/PR8 (IC50 = 2.93 µg/mL, SI = 294.85), A/Phil82 (IC50 = 1.42 µg/mL, SI = 608.38), and B/Yamagata (IC50 = 1.59 µg/mL, SI = 543.33). The antiviral action was found to occur in the post-entry stages of viral replication and to suppress viral replication by inducing apoptosis in infected cells. Moreover, it efficiently suppressed viral genome replication, protein synthesis, and infectivity in MDCK and A549 cells. Our findings highlight the antiviral capabilities of a novel marine bacterium, which could potentially be useful in the development of drugs for controlling viral diseases.
Assuntos
Herpesvirus Cercopitecino 1 , Influenza Humana , Viroses , Animais , Humanos , Influenza Humana/tratamento farmacológico , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Replicação ViralRESUMO
BACKGROUND: During the 2019 severe influenza season, New South Wales (NSW) experienced the highest number of cases in Australia. This study retrospectively investigated the genetic characteristics of influenza viruses circulating in NSW in 2019 and identified genetic markers related to antiviral resistance and potential virulence. METHODS: The complete genomes of influenza A and B viruses were amplified using reverse transcription-polymerase chain reaction (PCR) and sequenced with an Illumina MiSeq platform. RESULTS: When comparing the sequencing data with the vaccine strains and reference sequences, the phylogenetic analysis revealed that most NSW A/H3N2 viruses (n = 68; 94%) belonged to 3C.2a1b and a minority (n = 4; 6%) belonged to 3C.3a. These viruses all diverged from the vaccine strain A/Switzerland/8060/2017. All A/H1N1pdm09 viruses (n = 20) showed genetic dissimilarity from vaccine strain A/Michigan/45/2015, with subclades 6B.1A.5 and 6B.1A.2 identified. All B/Victoria-lineage viruses (n = 21) aligned with clade V1A.3, presenting triple amino acid deletions at positions 162-164 in the hemagglutinin protein, significantly diverging from the vaccine strain B/Colorado/06/2017. Multiple amino acid substitutions were also found in the internal proteins of influenza viruses, some of which have been previously reported in hospitalized influenza patients in Thailand. Notably, the oseltamivir-resistant marker H275Y was present in one immunocompromised patient infected with A/H1N1pdm09 and the resistance-related mutation I222V was detected in another A/H3N2-infected patient. CONCLUSIONS: Considering antigenic drift and the constant evolution of circulating A and B strains, we believe continuous monitoring of influenza viruses in NSW via the high-throughput sequencing approach provides timely and pivotal information for both public health surveillance and clinical treatment.
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Herpesvirus Cercopitecino 1 , Vacinas contra Influenza , Influenza Humana , Humanos , Estudos Retrospectivos , Herpesvirus Cercopitecino 1/genética , Vírus da Influenza A Subtipo H3N2/genética , New South Wales/epidemiologia , Filogenia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Austrália , Estações do Ano , Sequenciamento Completo do GenomaRESUMO
Two human patients with Macacine alphaherpesvirus 1 infection were identified in Japan in 2019. Both patients had worked at the same company, which had a macaque facility. The rhesus-genotype B virus genome was detected in cerebrospinal fluid samples from both patients.
Assuntos
Herpesvirus Cercopitecino 1 , Doenças dos Macacos , Animais , Humanos , Japão/epidemiologia , Macaca mulatta , GenótipoRESUMO
IMPORTANCE: Zoonotic infection of humans with herpes B virus (BV) causes severe neurological diseases. Acyclovir (ACV) and ganciclovir (GCV), most frequently used as anti-herpes drugs, are recommended for prophylaxis and therapy in human BV infection. In this study, we examined the property of BV thymidine kinase (TK) against anti-herpes drugs using a recombinant herpes simplex virus type 1 (HSV-1) carrying BV TK gene. We found that HSV-1 carrying BV TK was similarly sensitive to GCV as HSV-1 carrying varicella zoster virus TK. In addition, we demonstrated that BV TK was not mutated in the GCV- and ACV-resistant HSV-1 carrying BV TK, suggesting that ACV- or GCV-resistant BV might be rare during treatment with these antiviral drugs. These data can provide a new insight into the properties of BV TK in terms of the development of drug resistance.
Assuntos
Herpes Simples , Herpesvirus Cercopitecino 1 , Herpesvirus Humano 1 , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Herpesvirus Humano 1/genética , Timidina Quinase/genética , Timidina Quinase/uso terapêutico , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Ganciclovir/farmacologia , Herpes Simples/tratamento farmacológicoRESUMO
Baloxavir marboxil (baloxavir) is an FDA-approved inhibitor of the influenza virus polymerase acidic (PA) protein. Here, we used next-generation sequencing to compare the genomic mutational profiles of IAV H1N1 and H3N2, and IBV wild type (WT) and mutants (MUT) viruses carrying baloxavir resistance-associated substitutions (H1N1-PA I38L, I38T, and E199D; H3N2-PA I38T; and IBV-PA I38T) during passaging in normal human bronchial epithelial (NHBE) cells. We determined the ratio of nonsynonymous to synonymous nucleotide mutations (dN/dS) and identified the location and type of amino acid (AA) substitutions that occurred at a frequency of ≥30%. We observed that IAV H1N1 WT and MUT viruses remained relatively stable during passaging. While the mutational profiles for IAV H1N1 I38L, I38T, and E199D, and IBV I38T MUTs were relatively similar after each passage compared to the respective WTs, the mutational profile of the IAV H3N2 I38T MUT was significantly different for most genes compared to H3N2 WT. Our work provides insight into how baloxavir resistance-associated substitutions may impact influenza virus evolution in natural settings. Further characterization of the potentially adaptive mutations identified in this study is needed.
Assuntos
Herpesvirus Cercopitecino 1 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Tiepinas , Humanos , Oxazinas/farmacologia , Piridinas/farmacologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/metabolismo , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/metabolismo , Tiepinas/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Células Epiteliais/metabolismo , Genômica , Proteínas Virais/genética , NucleotidiltransferasesRESUMO
Herpes B virus is a biosafety level 4 pathogen and widespread in its natural host species, macaques. Although most infected monkeys show asymptomatic or mild symptoms, human infections with this virus can cause serious neurological symptoms or fatal encephalomyelitis with a high mortality rate. Herpes B virus can be latent in the sensory ganglia of monkeys and humans, often leading to missed diagnoses. Furthermore, the herpes B virus has extensive antigen crossover with HSV, SA8, and HVP-2, causing false-positive results frequently. Timely diagnosis, along with methods with sensitivity and specificity, are urgent for research on the herpes B virus. The lack of a clear understanding of the host invasion and life cycle of the herpes B virus has led to slow progress in the development of effective vaccines and drugs. This review discusses the research progress and problems of the epidemiology of herpes B virus, detection methods and therapy, hoping to inspire further investigation into important factors associated with transmission of herpes B virus in macaques and humans, and arouse the development of effective vaccines or drugs, to promote the establishment of specific pathogen-free (SPF) monkeys and protect humans to effectively avoid herpes B virus infection.
Assuntos
Infecções por Herpesviridae , Herpesvirus Cercopitecino 1 , Vacinas , Humanos , Animais , MacacaRESUMO
Macacine alphaherpesvirus 1, also known as herpes B virus (BV), is an alphaherpesvirus endemic to several macaque species, capable of causing zoonotic infections in humans, with high mortality rates. Evidence of reactivation in humans has rarely been reported. Here we depict a case of BV reactivation after 54 years, leading to severe meningoencephalitis. This case supports the use of antiviral prophylaxis in patients surviving a confirmed BV central nervous system infection. We sequenced DNA from BV obtained from the patient's cerebrospinal fluid. Phylogenetic analysis showed significant divergence in the clustering of this particular BV strain compared with other known BVs. Therefore, additional efforts are needed to obtain a broader sequence landscape from BVs circulating in monkeys.
Assuntos
Herpesvirus Cercopitecino 1 , Meningoencefalite , Animais , Humanos , Herpesvirus Cercopitecino 1/genética , Macaca , Meningoencefalite/complicações , Filogenia , Zoonoses , Feminino , IdosoRESUMO
BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Influenza A, and Influenza B viruses is essential for rapid differential diagnosis in patients with similar symptoms, especially during "flu season" in the post-pandemic era. So far, several multiplex methods have been approved for the simultaneous detection of SARS-CoV-2, Influenza A, and Influenza B. However, due to the rapid mutation rate of the SARS-CoV-2 genome and the emergence of new variants, existing methods must be improved and updated. METHODS: To identify a highly conserved region in the SARS-CoV-2 N-gene, a genomic survey was performed to increase the sensitivity and specificity of primer and probe sets targeting the SARS-CoV-2 genome. The 95% LLOD (95% lower limits of detection) were calculated by probit analysis. A total of 70 predetermined clinical samples using singleplex RT-qPCR assays, were included. The clinical performance of the multiplex RT-qPCR assay was determined and compared with a commercial multiplex kit. The Cohen's kappa coefficient, P-value (McNemar's test), Passing-Bablok regression, and Bland Altman agreement analysis were determined to monitor the agreement of the assays. RESULTS: The novel SARS-CoV-2 primer and probe set designed in this assay was able to detect all variants of concern (VOCs) and variants of interest (VOIs) with high analytical and clinical performance. The 95% LLOD for the multiplex RT-qPCR was 20 copies per reaction for the N gene of SARS-CoV-2, 2 copies per reaction for M1 gene of Influenza A and NS1 gene of Influenza B. The diagnostic sensitivity of the multiplex RT-qPCR was 94.4%, 93.7%, and 100% for the detection of SARS-CoV-2, Influenza A, and Influenza B genomes, respectively. Moreover, the specificity was identical (100%) in both assays. According to the agreement analysis results, there was no statistical difference between our multiplex assay and the commercial kit. CONCLUSIONS: In this study, we developed a novel in-house made multiplex RT-qPCR assay, with high sensitivity, specificity, and reliability for the diagnosis of SARS-CoV-2 infection in clinical samples. This is valuable during Influenza seasons when influenza co-circulates with SARS-CoV-2, as it saves costs, time, and thus specific and timely treatment of patients.
Assuntos
COVID-19 , Herpesvirus Cercopitecino 1 , Influenza Humana , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Influenza remains a worldwide health concern. Antiviral drugs are considered as one of the useful options for its prevention as a complementary measure to vaccination. Baloxavir acid selectively inhibits the cap-dependent endonuclease of influenza viruses and exhibits marked viral titre reduction in patients. Here, we describe the prophylactic potency of baloxavir acid against lethal infection with influenza A and B viruses in mice. BALB/c mice were subcutaneously administered once with baloxavir acid suspension, or orally administered once daily for 10 days with oseltamivir phosphate solution at human relevant doses. Next, the mice were intranasally inoculated with A/PR/8/34 (H1N1) or B/Hong Kong/5/72 strain at 24 to 96 h after the initial dosing. Prophylactic treatment with the antiviral drugs significantly reduced the lung viral titres and prolonged survival time. In particular, baloxavir acid showed a greater suppressive effect on lung viral titres compared to oseltamivir phosphate. In this model, baloxavir acid maintained significant prophylactic effects against influenza A and B virus infections when the plasma concentration at the time of infection was at least 0.88 and 3.58 ng/mL, respectively. The significant prophylactic efficacy observed in our mouse model suggests the potential utility of baloxavir marboxil for prophylaxis against influenza in humans.
Assuntos
Herpesvirus Cercopitecino 1 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Tiepinas , Humanos , Animais , Camundongos , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Oxazinas/uso terapêutico , Piridinas/uso terapêutico , Tiepinas/farmacologia , Tiepinas/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Camundongos Endogâmicos BALB C , FosfatosRESUMO
This study aims to develop a rapid and convenient test card for simultaneous detection of influenza A and influenza B viruses using quantum dot-based immunochromatographic assay. The test card consists of a test strip and a plastic casing. The test strip is composed of absorbent paper, a buffer pad, nitrocellulose membrane (NC membrane), sample pad, quantum dot-labeled antibody pad, and polyvinyl chloride (PVC) board. The NC membrane is coated with mouse monoclonal antibodies against influenza A and influenza B viruses for the T lines (test lines), and reference proteins A and B for the C line (control line). The quantum dot-labeled antibody pad contains mouse monoclonal antibody-quantum dot conjugates against influenza A and influenza B viruses. The results showed that the detection limit of the test card for both viruses ranged from 1.51 ×102 to 2.71×103 TCID50/ml, indicating its sensitivity for accurate detection of influenza A and influenza B viruses without being affected by various variants. The test card exhibited specific reactions with different subtypes of influenza A and influenza B virus culture fluids and showed no cross-reactivity with adenovirus, novel coronavirus, Mycoplasma pneumoniae, respiratory syncytial virus, Staphylococcus aureus, and other pathogens. Overall, the sensitivity and specificity of the test card for simultaneous detection of influenza A and influenza B viruses meet the requirements for clinical use. It offers the advantages of simplicity, rapidity, and no requirement for special equipment, enabling quick auxiliary diagnosis to prevent disease transmission.
Assuntos
COVID-19 , Herpesvirus Cercopitecino 1 , Influenza Humana , Animais , Camundongos , Humanos , Influenza Humana/diagnóstico , Sensibilidade e Especificidade , Vírus da Influenza BRESUMO
Influenza is a highly contagious respiratory illness that commonly causes outbreaks among human communities. Details about the exact nature of the droplets produced by human respiratory activities such as breathing, and their potential to carry and transmit influenza A and B viruses is still not fully understood. The objective of our study was to characterize and quantify influenza viral shedding in exhaled aerosols from natural patient breath, and to determine their viral infectivity among participants in a university cohort in tropical Singapore. Using the Gesundheit-II exhaled breath sampling apparatus, samples of exhaled breath of two aerosol size fractions ("coarse" > 5 µm and "fine" ≤ 5 µm) were collected and analyzed from 31 study participants, i.e., 24 with influenza A (including H1N1 and H3N2 subtypes) and 7 with influenza B (including Victoria and Yamagata lineages). Influenza viral copy number was quantified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Infectivity of influenza virus in the fine particle fraction was determined by culturing in Madin-Darby canine kidney cells. Exhaled influenza virus RNA generation rates ranged from 9 to 1.67 × 105 and 10 to 1.24 × 104 influenza virus RNA copies per minute for the fine and coarse aerosol fractions, respectively. Compared to the coarse aerosol fractions, influenza A and B viruses were detected more frequently in the fine aerosol fractions that harbored 12-fold higher viral loads. Culturable virus was recovered from the fine aerosol fractions from 9 of the 31 subjects (29%). These findings constitute additional evidence to reiterate the important role of fine aerosols in influenza transmission and provide a baseline range of influenza virus RNA generation rates.
Assuntos
Herpesvirus Cercopitecino 1 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Animais , Cães , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Singapura , Aerossóis e Gotículas Respiratórios , RNA Viral/genéticaRESUMO
Herpes B virus (BV) is a zoonotic virus which can be transmitted from macaques to humans, which is often associated with high mortality rates. Because macaques often exhibit asymptomatic infections, individuals who come into contact with these animals face unexpected risks of BV infections. A serological test is widely performed to investigate BV infections. However, the assay's sensitivity and specificity appeared to be inadequate, and it does not necessarily indicate ongoing viral shedding. Here, we developed LAMP and qPCR assays aiming to detect BVs with a high sensitivity and specificity in various macaque species and validated them using oral swab samples collected from 97 wild cynomolgus macaques living in Thailand. Our LAMP and qPCR assays detected more than 50 and 10 copies of the target sequences per reaction, respectively. The LAMP assay could detect BV within 25 min, indicating its advantages for the rapid detection of BV. Collectively, our findings indicated that both assays developed in this study exhibit advantages and usefulness for BV surveillance and the diagnosis of BV infections in macaques. Furthermore, for the first time, we determined the partial genome sequences of BVs detected in cynomolgus macaques in Thailand. Phylogenetic analysis revealed the species-specific evolution of BV within macaques.
Assuntos
Infecções por Herpesviridae , Herpesvirus Cercopitecino 1 , Humanos , Animais , Herpesvirus Cercopitecino 1/genética , Reação em Cadeia da Polimerase em Tempo Real , Filogenia , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/veterinária , Técnicas de Amplificação de Ácido Nucleico , Técnicas de Diagnóstico Molecular , Sensibilidade e Especificidade , Macaca fascicularisRESUMO
Boosting herpes simplex virus (HSV)-specific immunity in the genital tissues of HSV-positive individuals to increase control of HSV-2 recurrent disease and virus shedding is an important goal of therapeutic immunization and would impact HSV-2 transmission. Experimental therapeutic HSV-2 vaccines delivered by a parenteral route have resulted in decreased recurrent disease in experimental animals. We used a guinea pig model of HSV-2 infection to test if HSV-specific antibody and cell-mediated responses in the vaginal mucosa would be more effectively increased by intravaginal (Ivag) therapeutic immunization compared to parenteral immunization. Therapeutic immunization with HSV glycoproteins and CpG adjuvant increased glycoprotein-specific IgG titers in vaginal secretions and serum to comparable levels in Ivag- and intramuscular (IM)-immunized animals. However, the mean numbers of HSV glycoprotein-specific antibody secreting cells (ASCs) and IFN-γ SCs were greater in Ivag-immunized animals demonstrating superior boosting of immunity in the vaginal mucosa compared to parenteral immunization. Therapeutic Ivag immunization also resulted in a significant decrease in the cumulative mean lesion days compared to IM immunization. There was no difference in the incidence or magnitude of HSV-2 shedding in either therapeutic immunization group compared to control-treated animals. Collectively, these data demonstrated that Ivag therapeutic immunization was superior compared to parenteral immunization to boost HSV-2 antigen-specific ASC and IFN-γ SC responses in the vagina and control recurrent HSV-2 disease. These results suggest that novel antigen delivery methods providing controlled release of optimized antigen/adjuvant combinations in the vaginal mucosa would be an effective approach for therapeutic HSV vaccines. IMPORTANCE HSV-2 replicates in skin cells before it infects sensory nerve cells where it establishes a lifelong but mostly silent infection. HSV-2 occasionally reactivates, producing new virus which is released back at the skin surface and may be transmitted to new individuals. Some HSV-specific immune cells reside at the skin site of the HSV-2 infection that can quickly activate and clear new virus. Immunizing people already infected with HSV-2 to boost their skin-resident immune cells and rapidly control the new HSV-2 infection is logical, but we do not know the best way to administer the vaccine to achieve this goal. In this study, a therapeutic vaccine given intravaginally resulted in significantly better protection against HSV-2 disease than immunization with the same vaccine by a conventional route. Immunization by the intravaginal route resulted in greater stimulation of vaginal-resident, virus-specific cells that produced antibody and produced immune molecules to rapidly clear virus.
Assuntos
Herpes Genital , Herpes Simples , Herpesvirus Humano 2 , Animais , Feminino , Cobaias , Humanos , Adjuvantes Imunológicos , Anticorpos Antivirais , Glicoproteínas/metabolismo , Herpes Genital/prevenção & controle , Herpes Simples/metabolismo , Herpesvirus Cercopitecino 1 , Herpesvirus Humano 2/fisiologia , Imunização , Linfócitos T , Vagina/imunologia , Vagina/virologiaRESUMO
An estimated 257 million people are chronic carriers of hepatitis-B virus (HBV) infection, which resulted in around 1 million deaths, mainly due to hepatocellular carcinoma (HCC). Long-term nucleotide analog treatment of HBV infection is associated with favorable prognosis, no disease progression, and a reduction of HCC risk, but lifelong treatments are required. A better understanding of HBV replication cycle and the host immune response will likely improve the identification of new targets for drug development. Studies are ongoing to determine if it is possible to successfully combine direct-acting antivirals (DAA) with an immunomodulatory therapy to allow increased cure rates. This review will start with summarizing the HBV replication cycle, recall current treatments, and then discuss potential targets and antiviral approaches in development to optimistically reach the HBV cure.
Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Herpesvirus Cercopitecino 1 , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B/fisiologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Replicação ViralRESUMO
Neuraminidase inhibitors (NAIs) are recommended for influenza treatment and prevention worldwide. The most widely prescribed NAI is oral oseltamivir, while inhaled zanamivir is less commonly used. Using phenotypic neuraminidase (NA) enzymatic assays and molecular modeling approaches, we examined the ability of the investigational orally-dosed NAI AV5080 to inhibit viruses of the influenza A(H1N1)pdm09, A(H3N2), A(H5N1), and A(H7N9) subtypes and the influenza B/Victoria- and B/Yamagata-lineages containing NA substitutions conferring oseltamivir or zanamivir resistance including: NA-R292K, NA-E119G/V, NA-H274Y, NA-I122L/N, and NA-R150K. Broadly, AV5080 showed enhanced in vitro efficacy when compared with oseltamivir and/or zanamivir. Reduced AV5080 inhibition was determined for influenza A viruses with NA-E119G and NA-R292K, and for B/Victoria-lineage viruses with NA-I122N/L and B/Yamagata-lineage virus with NA-R150K. Molecular modeling suggested loss of the short hydrogen bond to the carboxyl group of AV5080 affected inhibition of NA-R292K viruses, whereas loss of the salt bridge with the guanidine group of AV5080 affected inhibition of NA-E119G. The resistance profiles and predicted binding modes of AV5080 and zanamivir are most similar, but dissimilar to those of oseltamivir, in part because of a guanidine moiety compensatory binding effect. Overall, our data suggests that AV5080 is a promising orally-dosed NAI that exhibited similar or superior in vitro efficacy against viruses with reduced or highly reduced inhibition phenotypes with respect to currently approved NAIs.
Assuntos
Herpesvirus Cercopitecino 1 , Vírus da Influenza A Subtipo H1N1 , Virus da Influenza A Subtipo H5N1 , Subtipo H7N9 do Vírus da Influenza A , Influenza Humana , Humanos , Antivirais/farmacologia , Farmacorresistência Viral/genética , Inibidores Enzimáticos/farmacologia , Guanidina/metabolismo , Guanidinas/metabolismo , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/virologia , Neuraminidase/genética , Oseltamivir/farmacologia , Zanamivir/farmacologiaRESUMO
Background: Hepatitis-B virus (HBV) co-infection among people living with HIV (PLWH) is highly endemic in South Africa. Despite the availability of an effective vaccine for the last four decades, chronic HBV infection is a major cause of morbidity and mortality among PLWH. Although the incidence of most opportunistic infections has been reduced in individuals with HIV since the implementation of the universal test and treat program in South Africa, HBV co-infection among PLWH is still accounting for high morbidity and mortality. Methodology: This cross-sectional descriptive survey was conducted in King Sabata Dalindyebo sub-district municipality in the Eastern Cape Province of South Africa to determine the prevalence of HBV co-infection among PLWH. Results: Two-thirds (65.5%) of the 602 PLWH who participated in the study had been screened for HBV co-infection. The mean age of the participants was 38.8±10.5 years and the majority (75.1%) were female. The prevalence of HBV co-infection among PLWH was 12.2%; among males were three times more frequently than females (OR=3, 95% CI 1.6-5.6, p=0.001). The median CD4 count of participants was 508 cell/mm3 (inter-quadrantile range = 307 to 715) and there was no significant association between HBV co-infection and CD4 count. Conclusion: There is a high prevalence of HBV co-infection among PLWH in the Mthatha region of South Africa. The high prevalence of HBV co-infection indicates the need for routine screening for hepatitis B among PLWH in South Africa.
Assuntos
Coinfecção , Infecções por HIV , Hepatite B , Herpesvirus Cercopitecino 1 , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Vírus da Hepatite B , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Prevalência , África do Sul/epidemiologia , Estudos Transversais , Coinfecção/epidemiologia , Hepatite B/complicaçõesRESUMO
BACKGROUND: Macacine alphaherpesvirus 1 (BV) was first reported in the 1930s and only about 60 cases have been diagnosed since then. METHODS: A 53-year-old male who worked as a veterinary surgeon, developed a fever with nausea and vomiting in April 2021 in Beijing, China. Real-time polymerase chain reaction (PCR) and metagenomics Next Generation Sequencing (mNGS) were used for diagnosis. RESULTS: BV DNA was confirmed by mNGS and PCR. The case died 51 days after onset, due to the damage to the brain and spinal cord caused by a viral infection and hypoxic-ischemic encephalopathy. The typical BV inclusion bodies in the brain were found for the first time. CONCLUSIONS: Here we reported the first human infection case of BV in China. This fatal case highlights the potential threat of BV to occupational workers and the essential role of surveillance.
Assuntos
Herpesvirus Cercopitecino 1 , Masculino , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real , Pequim , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Drugresistance in hepatitis B virus (HBV), especially due to prolonged treatment with nucleoside analogs, such as lamivudine (LAM), remains a clinical challenge. Alternatively, several plant products and isolated phytochemicals have been used as promising antiHBV therapeutics with no sign of resistance. Among all known Rhus species, R. coriaria, R. succedanea and R. tripartite have been widely studied for their antiHBV efficacy, however, the effects of R. retinorrhoea have not been previously investigated. The current study reported the isolation of two flavonoids, namely sakuranetin (SEK) and velutin (VEL), from the dichloromethane fraction of R. retinorrhoea aerial parts using chromatography and spectral analyses. The two flavonoids (6.2550 µg/ml) were pretested for nonhepatocytotoxicity using an MTT assay and their dose and timedependent inhibitory activities against HBV [hepatitis B surface antigen (HBsAg) and hepatitis B 'e' antigen (HBeAg)] in cultured HepG2.2.15 cells were assessed by ELISA. SEK and VEL at the selected doses (12.5 µg/ml) significantly inhibited HBsAg by ~58.8 and ~56.4%, respectively, and HBeAg by ~55.5 and ~52.4%, respectively, on day 5. The reference drugs LAM and quercetin (antiHBV flavonoids), suppressed the production of HBsAg/HBeAg by ~86.4/~64 and ~84.5/~62%, respectively. Furthermore, molecular docking of the flavonoids with HBV polymerase and capsid proteins revealed the formation of stable complexes with good docking energies, thus supporting their structurebased antiviral mechanism. In conclusion, the present study was the first to demonstrate the antiHBV therapeutic activities of SEK and VEL isolated from R. retinorrhoea.
Assuntos
Hepatite B Crônica , Herpesvirus Cercopitecino 1 , Rhus , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B , Herpesvirus Cercopitecino 1/metabolismo , Simulação de Acoplamento Molecular , Antivirais/farmacologia , Antivirais/uso terapêutico , Flavonoides/química , Vírus da Hepatite B/genética , Anticorpos/farmacologia , DNA ViralRESUMO
OBJECTIVE: To describe the anti-hepatitis B virus (HBV) efficacy, HBeAg serologic changes, HBV perinatal transmission, and safety in pregnant women who are living with human immunodeficiency virus (HIV) and HBV co-infection who were randomized to various antiretroviral therapy (ART) regimens. METHODS: The PROMISE (Promoting Maternal and Infant Survival Everywhere) trial was a multicenter randomized trial for ART-naive pregnant women with HIV infection. Women with HIV and HBV co-infection at 14 or more weeks of gestation were randomized to one of three ART arms: one without HBV treatment (group 1) and two HBV treatment arms with single (group 2) or dual anti-HBV activity (group 3). The primary HBV outcome was HBV viral load antepartum change from baseline (enrollment) to 8 weeks; safety assessments included alanine aminotransferase (ALT) level, aspartate aminotransferase (AST) level, and anemia (hemoglobin less than 10 g/dL). Primary comparison was for the HBV-active treatment arms. Pairwise comparisons applied t test and the Fisher exact tests. RESULTS: Of 3,543 women, 3.9% were HBsAg-positive; 42 were randomized to group 1, 48 to group 2, and 48 to group 3. Median gestational age at enrollment was 27 weeks. Among HBV-viremic women, mean antepartum HBV viral load change at week 8 was -0.26 log 10 international units/mL in group 1, -1.86 in group 2, and -1.89 in group 3. In those who were HBeAg-positive, HBeAg loss occurred in 44.4% at delivery. Two perinatal HBV transmissions occurred in group 2. During the antepartum period, one woman (2.4%) in group 1 had grade 3 or 4 ALT or AST elevations, two women (4.2%) in group 2, and three women (6.3%) in group 3. CONCLUSION: Over a short period of time, HBV DNA suppression was not different with one or two HBV-active agents. HbeAg loss occurred in a substantial proportion of participants. Perinatal transmission of HBV infection was low. Hepatitis B virus-active ART was well-tolerated in pregnancy, with few grade 3 or 4 ALT or AST elevations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT01061151.
Assuntos
Coinfecção , Infecções por HIV , Hepatite B Crônica , Hepatite B , Herpesvirus Cercopitecino 1 , Complicações Infecciosas na Gravidez , Lactente , Gravidez , Feminino , Humanos , Vírus da Hepatite B/genética , Infecções por HIV/tratamento farmacológico , Herpesvirus Cercopitecino 1/genética , Gestantes , Antígenos E da Hepatite B/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , HIV/genética , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Hepatite B/tratamento farmacológico , Parto , DNA Viral , Hepatite B Crônica/tratamento farmacológicoRESUMO
We evaluated the diagnostic performance of 4 commercially NAAT for detecting SARS-CoV-2 RNA, Influenza type A/B virus and RSV. Included tests were the Allplex™ SARS-CoV-2 fast PCR Assay (RNA extraction-free), Allplex™ RV Master Assay, Allplex™ SARS-CoV-2 fast MDx Assay (LAMP) and Aptima™ SARS-CoV-2/Flu Assay (RT-TMA). The assays' performance characteristics were determined using nasopharyngeal swabs from 270 patients with suspected SARS-CoV-2 infection. A total of 215 SARS-CoV-2 positive, 55 negative nasopharyngeal swabs and 19 bacteria strains were included. The sensitivities and specificities for detecting SARS-CoV-2, Influenza type A virus and RSV ranged between 81.8% and 100% with extremely good agreements (κ ≥ 86.8 %). The Aptima™ SARS-CoV-2/Flu Assay introduced a new result parameter, that is, TTime. Here, we showed that TTime may be used as a surrogate for Ct-value. We concluded that all assays assessed in this study can be used for routine detection of SARS-CoV-2, Influenza type A virus and RSV.