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The Journal of General Virology May 2024Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including...
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-1β, 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-β (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.
Topics: Animals; Horses; Herpesvirus 1, Equid; Female; Horse Diseases; Herpesviridae Infections; Cytokines; Antibodies, Viral; Virus Shedding; Viremia; Immunoglobulin G
PubMed: 38767608
DOI: 10.1099/jgv.0.001987 -
International Journal of Infectious... Aug 2024Encephalitis is a severe neurological syndrome for which herpesvirus and enteroviruses are the most common etiological agents. Arboviruses, a wildly diverse group of...
OBJECTIVES
Encephalitis is a severe neurological syndrome for which herpesvirus and enteroviruses are the most common etiological agents. Arboviruses, a wildly diverse group of pathogens, are also critical epidemiological agents associated with encephalitis. In Brazil, little is known about the causative agents of encephalitis.
METHODS
We conducted a hospital surveillance for encephalitis between 2020 and 2022. Molecular (RT-PCR and qPCR) and serological (virus-specific IgM and viral antigens) techniques were performed in cerebrospinal fluid and serum samples obtained from study participants.
RESULTS
In the 43 participants evaluated, the etiologic agent or the presence of IgM was detected in 16 (37.2%). Nine (20.9%) cases were positive for chikungunya virus (CHIKV), three (7.0%) for dengue virus, two (4.7%) for human adenovirus, one (2.3%) for varicella-zoster virus, and one (2.3%) for enterovirus. Whole-genome sequencing revealed that the CHIKV identified belongs to the East/Central/South African lineage.
CONCLUSION
Herein, CHIKV is a common pathogen identified in encephalitis cases. Our results reinforce previous evidence that chikungunya represents a significant cause of encephalitis during CHIKV outbreaks and epidemics and add to existing information on the epidemiology of encephalitis in Brazil.
Topics: Humans; Brazil; Chikungunya virus; Male; Female; Chikungunya Fever; Adult; Adolescent; Child; Young Adult; Middle Aged; Child, Preschool; Antibodies, Viral; Encephalitis, Viral; Immunoglobulin M; Aged; Dengue Virus; Infant; Phylogeny; Herpesvirus 3, Human; Enterovirus; Whole Genome Sequencing
PubMed: 38762045
DOI: 10.1016/j.ijid.2024.107090 -
Research in Veterinary Science Jul 2024Bovine alphaherpesvirus 1 (BoAHV-1) is the most important respiratory and reproductive disease-causing pathogen in dairy cattle. Despite BoAHV-1 has become widespread...
Bovine alphaherpesvirus 1 (BoAHV-1) is the most important respiratory and reproductive disease-causing pathogen in dairy cattle. Despite BoAHV-1 has become widespread and a major challenge to the dairy industry, little is known about its epidemiology in dairy herds in Ethiopia. A cross-sectional study was conducted from November 2022 to May 2023 to determine the seroprevalence and potential risk factors associated with BoAHV-1 seropositivity in dairy herds in North Shewa, the central highlands of Ethiopia. A total of 511 blood samples were collected from randomly selected cattle herds (n = 142) and examined antibodies against BoAHV-1 using ELISA test. A retrospective survey was also done to gather information related to reproductive disorders. The overall seroprevalence of BoAHV-1 was 61.84% (95% CI: 57.53-65.97) at the animal level and 85.21% (95% CI: 78.28-90.21) at the herd level. Multivariable logistic analysis revealed that the risk of being BoAHV-1 seropositive was nine times higher in cows older than six years (OR = 9.16; 95% CI: 3.09-27.16; P = 0.000), five times higher (OR = 4.51; 95% CI: 1.23-16.53; P = 0.019) in cows with a history of abortion, three times higher (OR = 2.75; 95% CI: 1.72-4.22; P = 0.029) in cows with a history of retained fetal membrane, and three times higher (OR = 2.83; 1.86-9.31; P = 0.03) in animals with clinical signs of ocular and/or nasal discharge. This study demonstrates a significant circulating of BoAHV-1 in the dairy cattle population in study districts. Thus, a comprehensive approach that includes strict farm biosecurity and vaccination should be practiced for effective BoAHV-1 control and prevention and to promote the growing dairy industry in the central highlands of Ethiopia.
Topics: Animals; Cattle; Ethiopia; Seroepidemiologic Studies; Cattle Diseases; Cross-Sectional Studies; Female; Herpesviridae Infections; Dairying; Risk Factors; Retrospective Studies; Antibodies, Viral; Herpesvirus 1, Bovine
PubMed: 38761676
DOI: 10.1016/j.rvsc.2024.105306 -
Journal of Virological Methods Jul 2024Primary cell cultures derived from human embryo lung play a crucial role in virology by aiding virus propagation and vaccine development. These cultures exhibit a...
Primary cell cultures derived from human embryo lung play a crucial role in virology by aiding virus propagation and vaccine development. These cultures exhibit a notable ability to undergo multiple subcultures, often reaching up to 70 passages. However, finding alternative primary cell cultures with similar longevity and usefulness is challenging. In this study, we introduce a novel primary culture cells derived from equine embryo brain (FEB), which cells exhibited remarkable long-term cultivation potential. The FEB was established and maintained using Sumitomo Nerve-Cell Culture System Comparison studies were conducted with fetal equine kidney cell line (FEK-Tc13) to assess growth rates and subculture longevity. Immunological characterization was performed using neuronal markers to confirm the neural nature of FEB cells. Viral growth assessments were conducted using equine herpesviruses (EHV-1 and EHV-4) to evaluate infectivity and cytopathic effects in FEB cells. PCR analysis and real-time PCR assays were employed to detect viral genomic DNA and transcription activity of EHVs in infected FEB cells. FEB cells demonstrated faster growth rates compared to fetal equine kidney cell line (FEK-Tc13 cells) and exhibited sustained subculture capability exceeding 50 passages. Immunostaining confirmed the glial identity of FEB cells. Both equine herpesviruses 1 and 4 EHV-1 and EHV-4 viruses efficiently replicated in FEB cells, resulting in clear cytopathic effects. PCR analysis detected genomic DNA of EHVs in infected FEB cells, indicating successful viral infection. The establishment of FEB cells with extended subculture capability highlights their potential utility as a model system for studying neural cell biology and viral infections.
Topics: Animals; Horses; Brain; Primary Cell Culture; Herpesvirus 1, Equid; Cell Line; Neurons; Virus Cultivation; Cell Culture Techniques; Cells, Cultured; Virus Replication
PubMed: 38754768
DOI: 10.1016/j.jviromet.2024.114952 -
Veterinary Microbiology Jul 2024Pig production is increasing annually in Africa as it is recognized as a significant source of income, livelihood and food security, particularly in rural communities.... (Review)
Review
Pig production is increasing annually in Africa as it is recognized as a significant source of income, livelihood and food security, particularly in rural communities. Understanding the circulating swine pathogens is crucial for the success of this emerging industry. Although there is extensive data available on the African swine fever virus due to its devastating impact on pig production, knowledge about the presence of other viral swine pathogens on the continent is still extremely limited. This review discusses what is currently known about six swine pathogens in Africa: classical swine fever virus, porcine reproductive and respiratory syndrome virus, porcine circovirus-2, porcine circovirus-3, porcine parvovirus-1, and pseudorabies virus. Gaps in our knowledge are identified and topics of future focus discussed.
Topics: Animals; Swine; Swine Diseases; Africa; Circovirus; Animals, Wild; Parvovirus, Porcine; Virus Diseases; Porcine respiratory and reproductive syndrome virus; African Swine Fever Virus; Animals, Domestic; Herpesvirus 1, Suid; Circoviridae Infections; Domestication
PubMed: 38749211
DOI: 10.1016/j.vetmic.2024.110120 -
Journal of Virology Jun 2024Equine herpesvirus type 1 (EHV-1) is a contagious respiratory pathogen that infects the mucosa of the upper respiratory tract (URT). Mucosal immune responses at the URT...
Equine herpesvirus type 1 (EHV-1) is a contagious respiratory pathogen that infects the mucosa of the upper respiratory tract (URT). Mucosal immune responses at the URT provide the first line of defense against EHV-1 and are crucial for orchestrating immunity. To define host-pathogen interactions, we characterized B-cell responses, antibody isotype functions, and EHV-1 replication of susceptible (non-immune) and clinically protected (immune) horses after experimental EHV-1 infection. Nasal secretion and nasal wash samples were collected and used for the isolation of DNA, RNA, and mucosal antibodies. Shedding of infectious virus, EHV-1 copy numbers, viral RNA expression, and host B-cell activation in the URT were compared based on host immune status. Mucosal EHV-1-specific antibody responses were associated with EHV-1 shedding and viral RNA transcription. Finally, mucosal immunoglobulin G (IgG) and IgA isotypes were purified and tested for neutralizing capabilities. IgG1 and IgG4/7 neutralized EHV-1, while IgG3/5, IgG6, and IgA did not. Immune horses secreted high amounts of mucosal EHV-1-specific IgG4/7 antibodies and quickly upregulated B-cell pathway genes, while EHV-1 was undetected by virus isolation and PCR. RNA transcription analysis reinforced incomplete viral replication in immune horses. In contrast, complete viral replication with high viral copy numbers and shedding of infectious viruses was characteristic for non-immune horses, together with low or absent EHV-1-specific neutralizing antibodies during viral replication. These data confirm that pre-existing mucosal IgG1 and IgG4/7 and rapid B-cell activation upon EHV-1 infection are essential for virus neutralization, regulation of viral replication, and mucosal immunity against EHV-1.IMPORTANCEEquine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion storms, and neurologic outbreaks known as equine herpes myeloencephalopathy (EHM). EHV-1 is transmitted with respiratory secretions by nose-to-nose contact or via fomites. The virus initially infects the epithelium of the upper respiratory tract (URT). Host-pathogen interactions and mucosal immunity at the viral entry site provide the first line of defense against the EHV-1. Robust mucosal immunity can be essential in protecting against EHV-1 and to reduce EHM outbreaks. It has previously been shown that immune horses do not establish cell-associated viremia, the prerequisite for EHM. Here, we demonstrate how mucosal antibodies can prevent the replication of EHV-1 at the epithelium of the URT and, thereby, the progression of the virus to the peripheral blood. The findings improve the mechanistic understanding of mucosal immunity against EHV-1 and can support the development of enhanced diagnostic tools, vaccines against EHM, and the management of EHV-1 outbreaks.
Topics: Animals; Herpesvirus 1, Equid; Horses; Virus Replication; Herpesviridae Infections; Antibodies, Viral; Antibodies, Neutralizing; Horse Diseases; Immunoglobulin G; Immunity, Mucosal; Virus Shedding; B-Lymphocytes; Host-Pathogen Interactions
PubMed: 38742875
DOI: 10.1128/jvi.00250-24 -
Journal of Neuro-ophthalmology : the... Jun 2024
Topics: Humans; Encephalitis, Varicella Zoster; Herpesvirus 3, Human; Magnetic Resonance Imaging; Ocular Motility Disorders; Video Recording
PubMed: 38741253
DOI: 10.1097/WNO.0000000000002026 -
Journal of Medical Virology May 2024The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real-world database from...
The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real-world database from the US community, this study spanning from 2006 to 2023, aimed to evaluate the impact of HZ vaccination on newly diagnosed diabetes patients who received an HZ vaccination within 1 year of diagnosis. Exclusion criteria were established to omit patients with immune deficiencies. The cohort consisted of 53 885 patients, with an average age of 63.5 years, including 43% females and 58% whites. After implementing 1:1 propensity score matching for age, sex, race, comorbidities, diabetes medication, and hemoglobin A1c to ensure comparability, the study population was further stratified into four groups: N1 comparing any HZ vaccination to non-HZ vaccination (53 882 matched pairs), N2 for Shingrix versus non-HZ vaccination (16 665 matched pairs), N3 for Zostavax versus non-HZ vaccination (12 058 matched pairs), and N4 for Shingrix versus Zostavax (11 721 matched pairs). Cox proportional hazards regression analysis revealed a hazard ratio (HR) for HZ incidence post any HZ vaccination of 0.92 (95% confidence interval [CI]: 0.83-1.01). Additional analyses yielded HRs of 1.12 (95% CI: 0.93-1.34) for Shingrix versus non-HZ vaccine, 1.02 (95% CI: 0.86-1.20) for Zostavax versus non-HZ vaccine, and 1.06 (95% CI: 0.87-1.29) for Shingrix versus Zostavax. Subgroup analyses across age, sex, and follow-up duration also showed no significant differences. These findings underscore the lack of a significant benefit from HZ vaccination in newly diagnosed diabetes patients aged over 50, highlighting the necessity for further prospective research.
Topics: Humans; Female; Male; Herpes Zoster Vaccine; Middle Aged; Herpes Zoster; Aged; Cohort Studies; Diabetes Mellitus; Vaccine Efficacy; Vaccination; Aged, 80 and over; Proportional Hazards Models; United States; Herpesvirus 3, Human
PubMed: 38738524
DOI: 10.1002/jmv.29667 -
Epidemiology and Infection May 2024Nosocomial outbreak of varicella zoster virus (VZV) has been reported when susceptible individuals encounter a case of chicken pox or shingles. A suspected VZV outbreak...
Nosocomial outbreak of varicella zoster virus (VZV) has been reported when susceptible individuals encounter a case of chicken pox or shingles. A suspected VZV outbreak was investigated in a 50-bedded in-patient facility of Physical Medicine and Rehabilitation in a tertiary care multispecialty hospital. A 30-year-old female patient admitted with Pott's spine was clinically diagnosed with chicken pox on 31 December 2022. The following week, four more cases were identified in the same ward. All cases were diagnosed as laboratory-confirmed varicella zoster infection by PCR. Primary case was a housekeeping staff who was clinically diagnosed with chicken pox 3 weeks prior (9 December 2022). He returned to work on eighth day of infection (17 December 2022) after apparent clinical recovery but before the lesions had crusted over. Thirty-one HCWs were identified as contacts a and three had no evidence of immunity. Two of these susceptible HCWs had onset of chickenpox shortly after first dose of VZV vaccination was inoculated. All cases recovered after treatment with no reported complications. VZV infection is highly contagious in healthcare settings with susceptible populations. Prompt identification of cases and implementation of infection prevention and control measures like patient isolation and vaccination are essential for the containment of outbreaks.
Topics: Humans; Disease Outbreaks; Tertiary Care Centers; Adult; Female; India; Cross Infection; Herpesvirus 3, Human; Male; Chickenpox; Long-Term Care; Varicella Zoster Virus Infection
PubMed: 38736415
DOI: 10.1017/S0950268824000712 -
Archives of Virology May 2024In this study, we investigated the role of serum/glucocorticoid-regulated kinase 1 (SGK1) in varicella-zoster virus (VZV) replication. VZV DNA replication and plaque...
In this study, we investigated the role of serum/glucocorticoid-regulated kinase 1 (SGK1) in varicella-zoster virus (VZV) replication. VZV DNA replication and plaque formation were inhibited by SGK1 knockout and treatment with an SGK1 inhibitor. Furthermore, SGK1 inhibition suppressed the increase in cyclin B1 expression induced by VZV infection. These results suggest that VZV infection induces SGK1 activation, which is required for efficient viral proliferation through the expression of cyclin B1. This is the first study to report that SGK1 is involved in the VZV life cycle.
Topics: Immediate-Early Proteins; Humans; Virus Replication; Herpesvirus 3, Human; Protein Serine-Threonine Kinases; Cyclin B1; Cell Line; DNA Replication
PubMed: 38722402
DOI: 10.1007/s00705-024-06051-1