Dynamics of simian immunodeficiency virus SIVmac239 infection in pigtail macaques
Nichole R Klatt1, Lauren A Canary, Thomas H Vanderford
1Laboratory of Molecular Microbiology and Program in Barrier Immunity and Repair, NIAID, NIH, Bethesda, Maryland, USA.
Abstract:
Pigtail macaques (PTM) are an excellent model for HIV research; however, the dynamics of simian immunodeficiency virus (SIV) SIVmac239 infection in PTM have not been fully evaluated. We studied nine PTM prior to infection, during acute and chronic SIVmac239 infections, until progression to AIDS. We found PTM manifest clinical AIDS more rapidly than rhesus macaques (RM), as AIDS-defining events occurred at an average of 42.17 weeks after infection in PTM compared to 69.56 weeks in RM (P = 0.0018). However, increased SIV progression was not associated with increased viremia, as both peak and set-point plasma viremias were similar between PTM and RM (P = 0.7953 and P = 0.1006, respectively). Moreover, this increased disease progression was not associated with rapid CD4(+) T cell depletion, as CD4(+) T cell decline resembled other SIV/human immunodeficiency virus (HIV) models. Since immune activation is the best predictor of disease progression during HIV infection, we analyzed immune activation by turnover of T cells by BrdU decay and Ki67 expression. We found increased levels of turnover prior to SIV infection of PTM compared to that observed with RM, which may contribute to their increased disease progression rate. These data evaluate the kinetics of SIVmac239-induced disease progression and highlight PTM as a model for HIV infection and the importance of immune activation in SIV disease progression.
Insights
Pigtail macaques (PTM) progress to simian immunodeficiency virus (SIV)-induced AIDS faster than rhesus macaques (RM). This accelerated disease in PTM is linked to higher pre-infection immune activation, not increased viral load or CD4+ T cell decline.
Area of Science:
- Comparative immunology
- Primate models of infectious disease
- Virology
Background:
- Pigtail macaques (PTM) are a valuable model for studying human immunodeficiency virus (HIV) infection.
- The specific dynamics of simian immunodeficiency virus (SIV) infection, particularly SIVmac239, in PTM require further investigation.
- Understanding SIV infection kinetics in different macaque species is crucial for advancing HIV/AIDS research.
Purpose of the Study:
- To evaluate the full dynamics of SIVmac239 infection in PTM.
- To compare the progression of SIVmac239 infection and AIDS development between PTM and rhesus macaques (RM).
- To investigate the role of immune activation in the accelerated disease progression observed in PTM.
Main Methods:
- Longitudinal study of nine PTM from pre-infection through SIVmac239 infection to AIDS progression.
- Comparison of AIDS-defining event timelines between PTM and RM.
- Analysis of plasma viremia (peak and set-point) and CD4+ T cell counts.
- Assessment of immune activation using T cell turnover markers (BrdU decay and Ki67 expression).
Main Results:
- PTM developed clinical AIDS significantly faster than RM (42.17 weeks vs. 69.56 weeks).
- Increased SIV progression in PTM was not associated with higher viremia or accelerated CD4+ T cell depletion compared to RM.
- PTM exhibited higher levels of T cell turnover prior to SIV infection compared to RM, suggesting pre-existing immune activation.
Conclusions:
- PTM manifest simian AIDS more rapidly than RM following SIVmac239 infection.
- Pre-infection immune activation in PTM may be a key factor driving faster disease progression.
- These findings underscore the importance of immune activation in SIV pathogenesis and highlight PTM as a relevant model for HIV research.
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