Evolution of viral life-cycle in response to cytotoxic T lymphocyte-mediated immunity.
Viruses in mammals are constantly faced with the problem of elimination by the host immunity. Cytotoxic T lymphocyte (CTL) responses are thought to play a major role in the control and clearance of several viral infections in mice and humans. It is therefore expected that over evolutionary time, viruses would be forced to evolve to avoid recognition by CTLs. Indeed, a number of studies have documented the accumulation of viral variants with escape mutations. These mutations allow viruses to hide from CTL responses common in the host population. CTLs recognize viruses by short protein sequences, named epitopes, derived from viral proteins. The efficiency of viral recognition by epitope-specific CTL responses depends on the expression pattern of the proteins carrying these epitopes, and the total amount of that protein (and thus epitopes) in the cell. When a virus replicates in a cell, some viral genes are expressed early in the life cycle of the virus, while other proteins are expressed late. For example, HIV infected cells first express Rev and Tat proteins, and the Gag proteins are expressed late. Here we propose a dynamical model of the viral life cycle to study how expression level of early vs. late genes may affect viral dynamics within the host and virus transmission over the course of infection. We find that for acute and chronic viral infections lower expression of early genes than that of the late genes is expected to give selective advantage and higher transmission to viruses.
Department of Mathematics and Gonda Brain Research Center, Bar-Ilan University, Ramat Gan 52900, Israel. louzouy@math.biu.ac.il
Yoram
Y
Louzoun
Vitaly V
VV
Ganusov
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003198:Computer Simulation; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D018448:Models, Immunological; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology / Q000821:virology; D014780:Viruses / Q000254:growth & development* / Q000276:immunology*