Murine gammaherpesvirus 68 bcl-2 homologue contributes to latency establishment in vivo.
The gammaherpesviruses are characteristically latent in lymphocytes and exploit lymphocyte proliferation to establish a large, persistent pool of latent genomes. Murine gammaherpesvirus 68 (MHV-68) allows the in vivo analysis of viral genes that contribute to this and other aspects of host colonization. In this study, the MHV-68 bcl-2 homologue, M11, was disrupted either in its BH1 homology domain or upstream of its membrane-localizing C-terminal domain. Each M11 mutant showed normal lytic replication in vitro and in vivo, but had a reduction in peak splenic latency. Lower infectious-centre titres correlated with lower in vivo B-cell activation, lower viral genome loads and reduced viral tRNA expression. This was therefore a true latency deficit, rather than a deficit in ex vivo reactivation. Stable, long-term levels of splenic latency were normal. M11 function therefore contributed specifically to viral latency amplification in infected lymphoid tissue.
de Lima
Brigitte D
BD
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
May
Janet S
JS
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Marques
Sofia
S
Laboratory of Microbiology, Faculty of Medicine, Lisbon University, Portugal.|Gulbenkian Institute for Science, 2780-156 Oeiras, Lisbon, Portugal.
Simas
J Pedro
JP
Laboratory of Microbiology, Faculty of Medicine, Lisbon University, Portugal.|Gulbenkian Institute for Science, 2780-156 Oeiras, Lisbon, Portugal.
Stevenson
Philip G
PG
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
D000818:Animals; D005260:Female; D006566:Herpesviridae Infections / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D018144:Rhadinovirus / Q000502:physiology*; D013154:Spleen / Q000821:virology; D014412:Tumor Virus Infections / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*; D017735:Virus Latency
C118862:M3 protein, Murine gammaherpesvirus; D014764:Viral Proteins