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1.
Int J Mol Sci ; 22(14)2021 Jul 13.
Article in English | MEDLINE | ID: mdl-34299120

ABSTRACT

The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. In this review, we will highlight the complex interplay between betaherpesviruses and the human immune response, focusing on protein function. We will explore methods by which the immune system first responds to betaherpesvirus infection as well as mechanisms by which viruses subvert normal cellular functions to evade the immune system and facilitate viral latency, persistence, and reactivation. Lastly, we will briefly discuss recent advances in vaccine technology targeting betaherpesviruses. This review aims to further elucidate the dynamic interactions between betaherpesviruses and the human immune system.


Subject(s)
Betaherpesvirinae/immunology , Betaherpesvirinae/pathogenicity , Herpesviridae Infections/virology , Immune Evasion , Immunity , Herpesviridae Infections/immunology , Humans
2.
Mol Cell ; 81(13): 2823-2837.e9, 2021 07 01.
Article in English | MEDLINE | ID: mdl-34015248

ABSTRACT

DNA-induced liquid-liquid phase separation of cyclic GMP-AMP synthase (cGAS) triggers a potent response to detect pathogen infection and promote innate immune signaling. Whether and how pathogens manipulate cGAS-DNA condensation to mediate immune evasion is unknown. We report the identification of a structurally related viral tegument protein family, represented by ORF52 and VP22 from gamma- and alpha-herpesvirinae, respectively, that employs a conserved mechanism to restrict cGAS-DNA phase separation. ORF52/VP22 proteins accumulate into, and effectively disrupt, the pre-formed cGAS-DNA condensation both in vitro and in cells. The inhibition process is dependent on DNA-induced liquid-liquid phase separation of the viral protein rather than a direct interaction with cGAS. Moreover, highly abundant ORF52 proteins carried within viral particles are able to target cGAS-DNA phase separation in early infection stage. Our results define ORF52/VP22-type tegument proteins as a family of inhibitors targeting cGAS-DNA phase separation and demonstrate a mechanism for how viruses overcome innate immunity.


Subject(s)
Alphaherpesvirinae , Betaherpesvirinae , DNA , Herpesviridae Infections , Immune Evasion , Nucleotidyltransferases , Viral Structural Proteins , Alphaherpesvirinae/chemistry , Alphaherpesvirinae/genetics , Alphaherpesvirinae/immunology , Betaherpesvirinae/chemistry , Betaherpesvirinae/genetics , Betaherpesvirinae/immunology , DNA/chemistry , DNA/genetics , DNA/immunology , HEK293 Cells , HeLa Cells , Herpesviridae Infections/genetics , Herpesviridae Infections/immunology , Humans , Immunity, Innate , Nucleotidyltransferases/chemistry , Nucleotidyltransferases/genetics , Nucleotidyltransferases/immunology , Viral Structural Proteins/chemistry , Viral Structural Proteins/genetics , Viral Structural Proteins/immunology
3.
PLoS One ; 10(2): e0116318, 2015.
Article in English | MEDLINE | ID: mdl-25658336

ABSTRACT

Asian elephant (Elephas maximus) immunity is poorly characterized and understood. This gap in knowledge is particularly concerning as Asian elephants are an endangered species threatened by a newly discovered herpesvirus known as elephant endotheliotropic herpesvirus (EEHV), which is the leading cause of death for captive Asian elephants born after 1980 in North America. While reliable diagnostic assays have been developed to detect EEHV DNA, serological assays to evaluate elephant anti-EEHV antibody responses are lacking and will be needed for surveillance and epidemiological studies and also for evaluating potential treatments or vaccines against lethal EEHV infection. Previous studies have shown that Asian elephants produce IgG in serum, but they failed to detect IgM and IgA, further hampering development of informative serological assays for this species. To begin to address this issue, we determined the constant region genomic sequence of Asian elephant IgM and obtained some limited protein sequence information for putative serum IgA. The information was used to generate or identify specific commercial antisera reactive against IgM and IgA isotypes. In addition, we generated a monoclonal antibody against Asian elephant IgG. These three reagents were used to demonstrate that all three immunoglobulin isotypes are found in Asian elephant serum and milk and to detect antibody responses following tetanus toxoid booster vaccination or antibodies against a putative EEHV structural protein. The results indicate that these new reagents will be useful for developing sensitive and specific assays to detect and characterize elephant antibody responses for any pathogen or vaccine, including EEHV.


Subject(s)
Antibodies, Anti-Idiotypic/immunology , Betaherpesvirinae/immunology , Elephants/immunology , Endangered Species , Herpesviridae Infections/prevention & control , Animals , Base Sequence , Chromatography, Gel , DNA Primers/genetics , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Herpesviridae Infections/immunology , Immunoglobulin A/genetics , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Immunoglobulin M/genetics , Immunoglobulin M/immunology , Molecular Sequence Data , Polymerase Chain Reaction , Sequence Analysis, DNA , Tandem Mass Spectrometry
4.
J S Afr Vet Assoc ; 79(1): 8-14, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18678185

ABSTRACT

There are at least 16 recognised herpesviruses that naturally infect cattle, sheep, goats and various species of deer and antelopes. Six of the viruses are recognised as distinct alphaherpesviruses and 9 as gammaherpesviruses. Buffalo herpesvirus (BflHV) and ovine herpesvirus-1 (OvHV-1) remain officially unclassified. The prevalence of ruminant herpesviruses varies from worldwide to geographically restricted in distribution. Viruses in both subfamilies Alphaherpesvirinae and Gammaherpesvirinae cause mild to moderate and severe disease in respective natural or secondary ruminant hosts. Accordingly, the economic and ecological impact of the viruses is also variable. The molecular characteristics of some members have been investigated in detail. This has led to the identification of virulence-associated genes and construction of deletion mutants and recombinant viruses. Some of the latter have been developed as commercial vaccines. This paper aims to give an overview of the epidemiology and pathogenesis of infection by these viruses, immuno-prophylaxis and mechanisms of recovery from infection. Since there are 128 ruminant species in the family Bovidae, it is likely that some herpesviruses remain undiscovered. We conclude that currently known ruminant alphaherpesviruses occur only in their natural hosts and do not cross stably into other ruminant species. By contrast, gammaherpesviruses have a much broader host range as evidenced by the fact that antibodies reactive to alcelaphine herpesvirus type 1 have been detected in 4 subfamilies in the family Bovidae, namely Alcelaphinae, Hippotraginae, Ovibovinae and Caprinae. New gammaherpesviruses within these subfamilies are likely to be discovered in the future.


Subject(s)
Alphaherpesvirinae/pathogenicity , Betaherpesvirinae/pathogenicity , Herpesviridae Infections/veterinary , Herpesviridae/pathogenicity , Herpesvirus Vaccines/immunology , Alphaherpesvirinae/immunology , Animals , Antelopes/virology , Betaherpesvirinae/immunology , Buffaloes/virology , Cattle , Cattle Diseases/epidemiology , Cattle Diseases/prevention & control , Deer/virology , Goat Diseases/epidemiology , Goat Diseases/prevention & control , Goats , Herpesviridae/immunology , Herpesviridae Infections/epidemiology , Herpesviridae Infections/prevention & control , Herpesvirus Vaccines/administration & dosage , Ruminants , Sheep , Sheep Diseases/epidemiology , Sheep Diseases/prevention & control , Species Specificity , Virulence/genetics
5.
Immunity ; 20(6): 656-8, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15189731

ABSTRACT

In this issue of Immunity, the Jonjic and Yokoyama teams provide evidence that beta-herpesvirus mutants can emerge under the selective pressure of innate immunity during primary infections. These rare mutants that escape natural killer cell recognition cause disease and death in mice that lack sterilizing T cell immunity.


Subject(s)
Betaherpesvirinae/immunology , Betaherpesvirinae/physiology , Immunity, Innate/immunology , Animals , Betaherpesvirinae/genetics , Humans , Killer Cells, Natural/immunology , Mutation/genetics , T-Lymphocytes/immunology
6.
Virus Res ; 55(1): 101-6, 1998 May.
Article in English | MEDLINE | ID: mdl-9712516

ABSTRACT

Two 18-month-old naturally reared ponies were used to investigate the pathogenicity of EHV-2. After dexamethasone treatment, pony 1 was inoculated intranasally with EHV-2 strain T16, which has been isolated from a foal with keratoconjunctivitis superficialis and pony 2 was similarly inoculated with strain LK4 which was originally isolated from a horse with upper respiratory tract disease. Following virus inoculation, pyrexia was not detected in either pony but both developed conjunctivitis, lymphadenopathy, and coughing. EHV-2 was detected in nasal mucus samples up to day 12 post infection (p.i.), in eye swabs up to day 10 p.i., and in buffy coat cells throughout the investigation in both animals. EHV-2-specific antibody titres were raised significantly 18 days p.i. Following the administration of dexamethasone, 3 months p.i., infectious virus was again detected in nasal mucus and conjunctival swabs from both ponies for 7 days. The tissue distribution of EHV-2 genome was studied post mortem, by means of a nested PCR. EHV-2 was detected in lymphoid tissues, lung, conjunctiva, trigeminal ganglia and olfactory lobes of pony 2, whereas in pony 1 only the conjunctiva of the left eye was PCR positive.


Subject(s)
Betaherpesvirinae/pathogenicity , Conjunctivitis, Viral/veterinary , Herpesviridae Infections/veterinary , Horse Diseases/virology , Animals , Antibodies, Viral/blood , Betaherpesvirinae/genetics , Betaherpesvirinae/immunology , Betaherpesvirinae/isolation & purification , Cells, Cultured , Conjunctivitis, Viral/immunology , Conjunctivitis, Viral/virology , DNA, Viral/analysis , Dexamethasone , Eye/virology , Herpesviridae Infections/immunology , Herpesviridae Infections/virology , Horse Diseases/immunology , Horses/virology , Lymphoid Tissue , Nerve Tissue , Nose/virology , Skin , Virus Shedding
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