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Updated: Apr 28, 2026
Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5α
Hadega A Aamer, Premeela Rajakumar, Julia Nyaundi
1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. mcorb@pitt.edu.
Background:
At least six host-encoded restriction factors (RFs), APOBEC3G, TRIM5α, tetherin, SAMHD1, schlafen 11, and Mx2 have now been shown to inhibit HIV and/or SIV replication in vitro. To determine their role in vivo in the resistance of macaques to mucosally-acquired SIV, we quantified both pre-exposure (basal) and post-exposure mRNA levels of these RFs, Mx1, and IFNγ in PBMC, lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal exposures to the primary isolate, SIV/DeltaB670.
Results:
Repetitive challenge divided the monkeys into two groups with respect to their susceptibility to infection: highly susceptible (2-3 challenges, 5 monkeys) and poorly susceptible (≥6 challenges, 3 monkeys). Basal RF and Mx1 expression varied among the three tissues examined, with the lowest expression generally detected in duodenal tissues, and the highest observed in PBMC. The one exception was A3G whose basal expression was greatest in lymph nodes. Importantly, significantly higher basal expression of TRIM5α and Mx1 was observed in PBMC of animals more resistant to mucosal infection. Moreover, individual TRIM5α levels were stable throughout a year prior to infection. Post-exposure induction of these genes was also observed after virus appearance in plasma, with elevated levels in PBMC and duodenum transiently occurring 7-10 days post infection. They did not appear to have an effect on control of viremia. Interestingly, minimal to no induction was observed in the resistant animal that became an elite controller.
Conclusions:
These results suggest that constitutively expressed TRIM5α appears to play a greater role in restricting mucosal transmission of SIV than that associated with type I interferon induction following virus entry. Surprisingly, this association was not observed with the other RFs. The higher basal expression of TRIM5α observed in PBMC than in duodenal tissues emphasizes the understated role of the second barrier to systemic infection involving the transport of virus from the mucosal compartment to the blood. Together, these observations provide a strong incentive for a more comprehensive examination of the intrinsic, variable control of constitutive expression of these genes in the sexual transmission of HIV.
Insights
Constitutively expressed TRIM5α, a host restriction factor, plays a key role in limiting mucosal simian immunodeficiency virus (SIV) transmission in macaques. Higher basal TRIM5α levels in peripheral blood mononuclear cells (PBMC) correlate with resistance to SIV infection.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Several host restriction factors (RFs) inhibit HIV/SIV replication in vitro.
- The in vivo role of RFs in macaque resistance to SIV is not fully understood.
Purpose of the Study:
- To investigate the role of RFs in vivo in rhesus macaque resistance to SIV.
- To quantify basal and post-exposure mRNA levels of RFs, Mx1, and IFNγ in different tissues.
Main Methods:
- Rhesus macaques were subjected to weekly low-dose rectal SIV exposures.
- mRNA levels of RFs, Mx1, and IFNγ were quantified in PBMC, lymph nodes, and duodenum.
- Monkeys were categorized based on susceptibility to SIV infection.
Main Results:
- Basal RF and Mx1 expression varied by tissue, with lowest levels in the duodenum.
- Higher basal TRIM5α and Mx1 expression in PBMC correlated with resistance to SIV.
- Post-exposure gene induction occurred but did not control viremia; minimal induction was seen in an elite controller.
Conclusions:
- Constitutively expressed TRIM5α is crucial for restricting SIV mucosal transmission.
- Higher basal TRIM5α in PBMC highlights its role as a barrier to systemic infection.
- Further research into constitutive gene expression control in HIV sexual transmission is warranted.
