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Herpes B virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class I expression in cells from human and macaque hosts.

ABSTRACT: B virus of the family Herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. Downregulation of major histocompatibility complex (MHC) class I in order to evade CD8(+) T-cell activation is characteristic of most herpesviruses. Here we examined the cell surface presence and total protein expression of MHC class I molecules in B virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are representative of foreign and natural host initial target cells of B virus. Our results show <20% downregulation of surface MHC class I molecules in either type of host cells infected with B virus, which is statistically insignificantly different from that observed in uninfected cells. We also examined the surface expression of MHC class Ib molecules, HLA-E and HLA-G, involved in NK cell inhibition. Our results showed significant upregulation of HLA-E and HLA-G in host cells infected with B virus relative to the amounts observed in other herpesvirus-infected cells. These results suggest that B virus-infected cell surfaces maintain normal levels of MHC class Ia molecules, a finding unique among simplex viruses. This is a unique divergence in immune evasion for B virus, which, unlike human simplex viruses, does not inhibit the transport of peptides for loading onto MHC class Ia molecules because B virus ICP47 lacks a transporter-associated protein binding domain. The fact that MHC class Ib molecules were significantly upregulated has additional implications for host-pathogen interactions.

SUBMITTER: Vasireddi M

PROVIDER: S-EPMC3497696 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Herpes B virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class I expression in cells from human and macaque hosts.

Vasireddi Mugdha M Hilliard Julia J

Journal of virology 20120912 23

B virus of the family Herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. Downregulation of major histocompatibility complex (MHC) class I in order to evade CD8(+) T-cell activation is characteristic of most herpesviruses. Here we examined the cell surface presence and total protein expression of MHC class I molecules in B virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are ...[more]

PMID: 22973043

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Project description:UnlabelledGlycoprotein D (gD) plays an essential role in cell entry of many simplexviruses. B virus (Macacine herpesvirus 1) is closely related to herpes simplex virus 1 (HSV-1) and encodes gD, which shares more than 70% amino acid similarity with HSV-1 gD. Previously, we have demonstrated that B virus gD polyclonal antibodies were unable to neutralize B virus infectivity on epithelial cell lines, suggesting gD is not required for B virus entry into these cells. In the present study, we confirmed this finding by producing a B virus mutant, BV-ΔgDZ, in which the gD gene was replaced with a lacZ expression cassette. Recombinant plaques were selected on complementing VD60 cells expressing HSV-1 gD. Virions lacking gD were produced in Vero cells infected with BV-ΔgDZ. In contrast to HSV-1, B virus lacking gD was able to infect and form plaques on noncomplementing cell lines, including Vero, HEp-2, LLC-MK2, primary human and macaque dermal fibroblasts, and U373 human glioblastoma cells. The gD-negative BV-ΔgDZ also failed to enter entry-resistant murine B78H1 cells bearing a single gD receptor, human nectin-1, but gained the ability to enter when phenotypically supplemented with HSV-1 gD. Cell attachment and penetration rates, as well as the replication characteristics of BV-ΔgDZ in Vero cells, were almost identical to those of wild-type (wt) B virus. These observations indicate that B virus can utilize gD-independent cell entry and transmission mechanisms, in addition to generally used gD-dependent mechanisms.ImportanceB virus is the only known simplexvirus that causes zoonotic infection, resulting in approximately 80% mortality in untreated humans or in lifelong persistence with the constant threat of reactivation in survivors. Here, we report that B virus lacking the gD envelope glycoprotein infects both human and monkey cells as efficiently as wild-type B virus. These data provide evidence for a novel mechanism(s) utilized by B virus to gain access to target cells. This mechanism is different from those used by its close relatives, HSV-1 and -2, where gD is a pivotal protein in the virus entry process. The possibility remains that unidentified receptors, specific for B virus, permit virus entry into target cells through gD-independent pathways. Understanding the molecular mechanisms of B virus entry may help in developing rational therapeutic strategies for the prevention and treatment of B virus infection in both macaques and humans.

Dataset Information

Herpes B virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class I expression in cells from human and macaque hosts.

Publications

Herpes B virus, macacine herpesvirus 1, breaks simplex virus tradition via major histocompatibility complex class I expression in cells from human and macaque hosts.

Similar Datasets

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