Gammaherpesvirinae

Subfamily of viruses

Gammaherpesvirinae is a subfamily of viruses in the order Herpesvirales and in the family Herpesviridae. Viruses in Gammaherpesvirinae are distinguished by reproducing at a more variable rate than other subfamilies of Herpesviridae. Mammals serve as natural hosts. There are 43 species in this subfamily, divided among 7 genera with three species unassigned to a genus. Diseases associated with this subfamily include: HHV 4: infectious mononucleosis. HHV 8: Kaposi's sarcoma.

Herpesviruses represent a group of double stranded DNA viruses distributed widely within the animal kingdom. The family Herpesviridae, which contains eight viruses that infect humans, is the most extensively studied group within this order and comprises three subfamilies, namely Alphaherpesvirinae, Betaherpesvirinae and Gammaherpesvirinae. Within the Gammaherpesvirinae there are a number of unclassified viruses including Cynomys herpesvirus 1 (CynGHV 1) Elephantid herpesvirus 3, Elephantid herpesvirus 4, Elephantid herpesvirus 5, Procavid herpesvirus 1, Trichechid herpesvirus 1 and Common bottlenose dolphin gammaherpesvirus 1.

Gammaherpesvirinae consists of the following seven genera: Therefore, the least contribution to pathogenicity has to be expected from this stage. The ORFs expressed during that stage are further divided into immediate early, early, and late. Promoter activation mediated by these proteins has also a strong effect on DNA synthesis from the origins of lytic DNA replication. As a result, virions are generated and released from the productively infected cells.

Viruses that establish lifelong latent infections must ensure that the viral genome is maintained within the latently infected cell throughout the life of the host, yet at the same time must also be capable of avoiding elimination by the immune surveillance system especially must avoid being detected by host CD8+ cytotoxic T lymphocytes (CTLs). The gamma herpesviruses are characteristically latent in lymphocytes and drive the proliferation that requires the expression of latent viral antigens. The majority of gammaherpesviruses encode a specific protein that is critical for maintenance of the viral genome within latently infected cells termed the genome maintenance protein (GMP). During latency, the genome persists in the nucleus of the infected cells as a circular episomal element. GMPs are DNA binding proteins that ensure that, as the host cell progresses through mitosis, the viral episomes are partitioned to daughter cells. This provides continuous existence of the viral genome within the host cells. MHV68 in genetically modified mice is used as a model for studying infection and host responses. Stable lifelong latency is a hallmark of the chronic phase of MHV68 infection. The spleen is a major infection site. The episomal maintenance protein for MHV68 is a latency associated nuclear antigen (mLANA; ORF73). M2 protein mediates signaling pathways of infected B cells by interacting with SH2 and SH3 containing proteins. Host factors have been identified that can promote or antagonize MHV68 latency and reactivation. Murid herpesvirus 68 is an important model system for the study of gammaherpesviruses with tractable genetics. The gammaherpesviruses, including HVS, EBV, KSHV, and RRV, are capable of establishing latent infection in lymphocytes. Attenuated virus mutants represent a promising approach towards gamma herpesvirus infection control. Surprisingly, latency deficient and, therefore, apathogenic MHV 68 mutants are found to be highly effective vaccines against these viruses. Research in this area is almost exclusively performed using MHV68 as KSHV and EBV (the major human pathogens of this family) do not productively infect model organisms typically used for this type of experimentation.

Herpesviruses have large genomes containing a wide array of genes. Although the first ORF in these gammaherpesviruses have oncogenic potential, other viral genes may also play a role in viral transformation. A striking feature of the four gammaherpesviruses is that they contain distinct ORFs involved in lymphocyte signaling events. At the left end of each viral genome are located ORFs encoding distinct transforming proteins. Gammaherpesvirus genes are capable of modulating cellular signals such that cell proliferation and viral replication occur at the appropriate times in the viral life cycle.