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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Primary simian immunodeficiency virus SIVmnd-2 infection in mandrills (Mandrillus sphinx)
Richard Onanga1, Sandrine Souquière, Maria Makuwa
1Département de Virologie, Centre International de Recherche Médicales, Gabon. onangar@yahoo.com
Abstract:
Mandrills are the only nonhuman primate (NHP) naturally infected by two types of simian immunodeficiency virus (SIV): SIVmnd-1 and SIVmnd-2. We have already reported that the high SIVmnd-1 replication during primary infection contrasts with only transient changes in CD4+ and CD8+ cell counts. Since early virus-host interactions predict viral control and disease progression in human immunodeficiency virus-infected patients, we investigated the dynamics of SIVmnd-2 primary infection in mandrills to examine the impact on immune effectors in blood and lymph nodes (LNs). To avoid in vitro strain selection, all mandrills in this study received plasma from SIVmnd-2-infected mandrills. SIVmnd-2 plasma viremia peaked at 10(7) to 10(8) RNA copies/ml between days 7 and 10. This peak was followed in all four monkeys by a decline in virus replication, with a set point level of 10(5) to 10(6) RNA copies/ml at day 42 postinfection (p.i.). Viral DNA load in PBMC and LNs also peaked between days 7 and 10 (10(5) to 10(6) DNA copies/10(6) cells) and stabilized at 10(3) to 10(4) DNA copies/10(6) cells during the chronic phase. Anti-SIVmnd-2 antibodies were detected starting from days 28 to 32. A transitory decline of CD3+ CD4+ cells in the LNs occurred in animals with high peak VLs. CD4+ and CD8+ T-cell activation in blood and LNs was noted between days 5 and 17 p.i., surrounding the peak of viral replication. This was most significant in the LNs. Activation markers then returned to preinfection values despite continuous and active viral replication during the chronic infection. The dynamics of SIVmnd-2 infection in mandrills showed a pattern similar to that of SIVmnd-1 infection. This might be a general feature of nonpathogenic SIV natural African NHP models.
Insights
Mandrills infected with simian immunodeficiency virus (SIV) show controlled viral replication and transient immune cell changes. This nonhuman primate model offers insights into early virus-host interactions relevant to human immunodeficiency virus.
Area of Science:
- Primate immunology
- Virology
- Infectious disease modeling
Background:
- Mandrills are unique nonhuman primates (NHPs) naturally infected with two simian immunodeficiency virus (SIV) types: SIVmnd-1 and SIVmnd-2.
- Previous studies showed high SIVmnd-1 replication with only transient CD4+ and CD8+ T-cell count changes.
- Early virus-host interactions are critical for predicting viral control and disease progression in human immunodeficiency virus (HIV) infection.
Purpose of the Study:
- To investigate the immune dynamics during primary SIVmnd-2 infection in mandrills.
- To assess the impact of SIVmnd-2 on immune effectors in blood and lymph nodes (LNs).
- To compare SIVmnd-2 infection patterns with SIVmnd-1 in this NHP model.
Main Methods:
- Mandrills were infected with plasma from SIVmnd-2-infected animals to avoid in vitro strain selection.
- Viral load (plasma viremia, viral DNA in PBMCs and LNs) was monitored post-infection.
- CD4+ and CD8+ T-cell counts and activation markers in blood and LNs were analyzed.
Main Results:
- SIVmnd-2 plasma viremia peaked at days 7-10 (10^7–10^8 RNA copies/ml), followed by a decline to a set point of 10^5–10^6 RNA copies/ml.
- Viral DNA loads in PBMCs and LNs peaked similarly and stabilized during the chronic phase.
- Transient CD4+ T-cell decline in LNs was observed in animals with high peak viral loads; T-cell activation peaked around viral load peaks and returned to baseline.
Conclusions:
- SIVmnd-2 primary infection in mandrills is characterized by high initial viral replication followed by controlled viremia.
- Immune activation is transient and correlates with viral replication peaks, similar to SIVmnd-1 infection.
- The dynamics suggest that nonpathogenic SIV infection in African NHPs may follow a general pattern, providing valuable models for studying lentiviral infections.
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