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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
Viral Envelope Evolution in Simian-HIV-Infected Neonate and Adult-Dam Pairs of Rhesus Macaques
Elena E Giorgi1, Hui Li2, Bhavna Hora3
1Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Neonatal Simian-HIV infection in rhesus macaques leads to more broadly neutralizing antibodies (bNAbs) than in adults. Increased viral diversity in neonates drives this enhanced bNAb development, offering insights for pediatric HIV vaccine strategies.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Simian-HIV (SHIV) infection in rhesus macaques (RMs) can elicit HIV-1 neutralizing antibodies (NAbs).
- Neonate RMs previously showed a higher frequency of generating broadly neutralizing antibodies (bNAbs) compared to their dams.
Purpose of the Study:
- To characterize the genetic diversity of Simian-HIV Env sequences in neonate and adult/dam RM pairs.
- To correlate viral genetic diversity with the development of heterologous HIV-1 NAbs.
Main Methods:
- Phylogenetic analysis of longitudinal Env sequences from four RM pairs (neonate/dam).
- Sequence diversity analysis to identify variable Env sites associated with NAb development.
Main Results:
- Higher genetic diversity within hosts correlated with heterologous HIV-1 NAb development.
- Identified 22 Env variable sites, with 9 associated with heterologous NAb development, including 3 with known bNAb-linked mutations.
- Neonate RMs showed faster accumulation of viral diversity, potentially explaining enhanced bNAb induction.
Conclusions:
- Viral diversity is a key driver of heterologous HIV-1 NAb development.
- Faster viral evolution in neonates may underlie enhanced bNAb induction in pediatric populations.
- Findings can inform the design of Env immunogens for HIV vaccines targeting bNAb development.
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