Abstract
Gammaherpesviruses are important pathogens that establish latent infection in their natural host for lifelong persistence. During latency, the viral genome persists in the nucleus of infected cells as a circular episomal element while the viral gene expression program is restricted to non-coding RNAs and a few latency proteins. Among these, the genome maintenance protein (GMP) is part of the small subset of genes expressed in latently infected cells. Despite sharing little peptidic sequence similarity, gammaherpesvirus GMPs have conserved functions playing essential roles in latent infection. Among these functions, GMPs have acquired an intriguing capacity to evade the cytotoxic T cell response through self-limitation of MHC class I-restricted antigen presentation, further ensuring virus persistence in the infected host. In this review, we provide an updated overview of the main functions of gammaherpesvirus GMPs during latency with an emphasis on their immune evasion properties.
Highlights
Herpesviruses are enveloped double-stranded DNA viruses that are in general responsible for persistent infections in a large number of animal species
In 2008, the International Committee on Taxonomy of Viruses (ICTV) created the order Herpesvirales comprising three families: the family Malacoherpesviridae composed of viruses infecting molluscs such as oysters, the family Alloherpesviridae composed of viruses infecting fish species and amphibians, and the predominantly studied family Herpesviridae that includes viruses of mammals and birds, itself classified into the three subfamilies Alpha, Beta, and Gammaherpesvirinae
The main objective of this review is to briefly summarize the importance of gammaherpesvirus infections and how genome maintenance protein (GMP) maintain viral episomes in infected lymphocytes, before focusing on a more detailed description of the mechanisms mediated by GMPs to escape immune surveillance, in particular CD8+ cytotoxic T cells (CTLs), during latent infection
Summary
Herpesviruses are enveloped double-stranded DNA viruses that are in general responsible for persistent infections in a large number of animal species. A hallmark of all herpesviruses is their unique capacity to induce lifelong infection through establishing and maintaining latent infection. The definition of herpesvirus latency involves: (i) the presence of the viral genome in the nucleus of the infected cell (either as an episome or integrated in cellular chromosomes), (ii) reduced viral gene expression together with the absence of virion production, and (iii) the ability of latently infected cells to reactivate lytic viral replication either in vivo and/or in vitro (Lieberman, 2016). Latent lifelong infection requires evasion mechanisms from the host immune response. Most alphaherpesviruses such as herpes simplex virus (HSV-1 or human alphaherpesvirus 1 – HHV-1) establish latency in non-dividing sensory
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