title: Vaccination-induced noncytolytic effects in the acute phase of SHIV infection.
abstract: Many studies have shown that vaccines inducing CD8+ T cell responses can reduce viral loads and preserve CD4+ T cell numbers in monkey models of HIV infection. The mechanism of viral control by the vaccine-induced CD8+ T cells is usually assumed to be cytolysis of infected cells. However, in addition to cytolysis of infected cells, CD8+ T cells secrete a range of soluble factors that suppress viral replication. We have studied the dynamics of virus and CD4+ T cells in a successful vaccination-challenge model of SHIV infection. We find that better viral control in the acute phase of infection is associated with slower decay of peak viral load. Comparing viral and CD4+ T cell dynamics in acute infection, we find that a cytolytic mode of viral control with direct killing of infected cells is inconsistent with the observed trends. On the other hand, comparison of the predicted effects of noncytolytic CD8+ effector function with the experimental data shows that non-cytolytic control provides a better explanation of the experimental results. Our analysis suggests that vaccine-induced CD8+ T cells control SHIV infection by non-cytolytic means.
authors.affiliation: Complex Systems in Biology Group, Centre for Vascular Research, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Janka
authors.initials: J
authors.lastname: Petravic
authors.forename: Miles P
authors.initials: MP
authors.lastname: Davenport
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D006801:Humans; D007700:Kinetics; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D018448:Models, Immunological; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination; D019562:Viral Load / Q000276:immunology*