Susceptibility to repeated, low-dose, rectal SHIVSF162P3 challenge is independent of TRIM5 genotype in rhesus...

Area of Science:

• Virology
• Immunology
• Primatology

Background:

• Repeated, low-dose (RLD) mucosal simian-human immunodeficiency virus (SHIV) exposures in macaques are a key model for testing HIV biomedical prevention strategies.
• Animal susceptibility variations can complicate study designs, necessitating an understanding of genetic factors influencing infection.
• TRIM5 alleles (Q, CypA, TFP) are known resistance factors for certain SHIV strains in rhesus macaques, but their impact on SIVmac239-derived SHIVSF162P3 requires further investigation.

Purpose of the Study:

• To evaluate the influence of TRIM5 genotype on susceptibility to rectal RLD SHIVSF162P3 infection in Indian rhesus macaques.
• To assess the impact of TRIM5 genotype on plasma viremia following SHIVSF162P3 infection in a rectal RLD model.
• To determine the suitability of SHIVSF162P3 for RLD experimentation by examining TRIM5 allele effects.

Main Methods:

• Analysis of 43 male Indian rhesus macaques from control arms of completed studies.
• Assessment of TRIM5 genotypes (Q, CypA, TFP) in relation to SHIVSF162P3 infection following rectal RLD exposures.
• Quantification of plasma viremia (viral copies/ml) in infected animals.

Main Results:

• The median number of exposures required for infection was similar across different TRIM5 genotypes (Q/Q: 3, Q/CypA: 4, TFP/Q: 3, TFP/TFP: 3, TFP/CypA: 2).
• Median peak viremia levels were comparable among infected macaques with different TRIM5 genotypes (Q/Q: 7.4, Q/CypA: 7.2, TFP/Q: 7.3, TFP/TFP: 7.1, TFP/CypA: 6.5 log10 viral copies/ml).
• Statistical analyses (log rank test, Kruskal-Wallis test) revealed no significant differences in susceptibility or peak viremia based on TRIM5 genotype, with limitations due to sample size for certain genotypes.

Conclusions:

• Rhesus macaque susceptibility to rectal RLD SHIVSF162P3 infection and subsequent plasma viremia are independent of TRIM5 TFP, CypA, and Q alleles.
• The study's power to detect effects of CypA/CypA and TFP/CypA genotypes was limited due to their absence or low frequency in the study population.
• SHIVSF162P3 is suitable for repeated, low-dose (RLD) mucosal infection models, as TRIM5 alleles do not restrict infection or replication rates, supporting its use in HIV prevention research.