HIV-1-specific CD8+ T cell responses during primary infection are major determinants of the viral set point and loss of CD4+ T cells. - Related Articles
HIV-1-specific CD8+ T cell responses during primary infection are major determinants of the viral set point and loss of CD4+ T cells.
J Virol. 2009 May 20;
Authors: Streeck H, Jolin JS, Qi Y, Yassine-Diab B, Johnson RC, Kwon DS, Addo MM, Brumme C, Routy JP, Little S, Jessen HK, Kelleher AD, Hecht FM, Sekaly RP, Rosenberg ES, Walker BD, Carrington M, Altfeld M
Primary HIV-1 infection (PHI) is marked by a flu-like syndrome and high levels of viremia that decrease to a viral set point with the first emergence of virus-specific CD8+ T cell responses. Here we investigated in a large cohort of 527 subjects the immunodominance pattern of the first virus-specific CTL responses developed during PHI in comparison to CTL responses in chronic infection, and demonstrate a distinct relationship between the early virus-specific CTL responses and viral set point as well as the slope of CD4+ decline. CTL responses during PHI followed clear hierarchical immunodominance patterns that were lost during the transition to chronic infection. Importantly, the immunodominance patterns of HIV-1-specific CTL responses detected in primary, but not in chronic HIV-1 infection, were significantly associated with the subsequent set point of viral replication. Moreover, the preservation of the initial CD8+ T cell immunodominance patterns from the acute into the chronic phase of infection was significantly associated with slower CD4+ T cell decline. Taken together, these data show that the specificity of the initial CTL response to HIV is critical for the subsequent control of viremia, and have important implications for the rational selection of antigens for future HIV-1 vaccines.
PMID: 19458000 [PubMed - as supplied by publisher] [PubMed-HIV]