Role of CD8 super(+) Lymphocytes in Control of Simian Immunodeficiency Virus Infection and Resistance to Rechallenge after Transient Early Antiretroviral Treatment

• Published in: Journal of virology 2001-11, Vol.75 (21), p.10187-10199
• Main Authors: Lifson, J D, Rossio, J L, Piatak Jr, M, Parks, T, Li, L, Kiser, R, Coalter, V, Fisher, B, Flynn, B M, Czajak, S, Hirsch, V M, Reimann, KA, Schmitz, JE, Ghrayeb, J, Bischofberger, N, Nowak, MA, Desrosiers, R C, Wodarz, D
• Format: Article
• Language: English
• Subjects: (R)-9-(2-phosphonylmethoxypropyl)adenine; antiretroviral agents; antiretroviral therapy; CD8 antigen; Human immunodeficiency virus; Macaca mulatta; Simian immunodeficiency virus; tenofovir
• ISSN: 0022-538X
• DOI: 10.1128/JVI.75.21.10187-10199.2001

Transient antiretroviral treatment with tenofovir, (R)-9-(2-phosphonylmethoxypropyl)adenine, begun shortly after inoculation of rhesus macaques with the highly pathogenic simian immunodeficiency virus (SIV) isolate SIVsmE660, facilitated the development of SIV-specific lymphoproliferative responses and sustained effective control of the infection following drug discontinuation. Animals that controlled plasma viremia following transient postinoculation treatment showed substantial resistance to subsequent intravenous rechallenge with homologous (SIVsmE660) and highly heterologous (SIVmac239) SIV isolates, up to more than 1 year later, despite the absence of measurable neutralizing antibody. In some instances, resistance to rechallenge was observed despite the absence of detectable SIV-specific binding antibody and in the face of SIV lymphoproliferative responses that were low or undetectable at the time of challenge. In vivo monoclonal antibody depletion experiments demonstrated a critical role for CD8 super(+) lymphocytes in the control of viral replication; plasma viremia rose by as much as five log units after depletion of CD8 super(+) cells and returned to predepletion levels (as low as