Mimicking SIV chimpanzee viral evolution toward HIV-1 during cross-species transmission

Abstract

HIV-1 evolved from SIV during cross-species transmission events, though viral genetic changes are not well understood. Here, we studied the evolution of SIVcpzLB715 into HIV-1 Group M using humanized mice. High viral loads, rapid CD4⁺ T-cell decline, and non-synonymous substitutions were identified throughout the viral genome suggesting viral adaptation.

Keywords: Cross‐species SIV transmission; HIV‐1 viral evolution from SIV; SIV chimpanzee evolution toward HIV‐1; SIVcpz infection in humanized mice; hu‐HSC mice for cross‐species viral transmission.

Figure 1.. SIVcpzLB715 infection kinetics during the second generation in hu-HSC mice.

(A) Experimental scheme for SIVcpzLB715 infection of hu-HSC mice. Neonatal mice are sublethally irradiated and inoculated intrahepatically with CD34⁺ hematopoietic stem cells. Following SIVcpzLB715 inoculation, PVL were assessed weekly and CD4⁺ T-cell decline bimonthly. (B) Second generation PVL and CD4⁺ T-cell decline seen in SIVcpzLB715 infected hu-HSC mice. Statistically significant CD4⁺ T-cell depletion occurred by the end of the second generation in infected mice relative to the uninfected mice (two-tailed Student’s t-test, *p<0.001).

Figure 2.. BLOSUM62 matrix scores of identified residue changes.

Variant residues were identified as described in the results and methods. Some variants in Vpr, Vpu and Env appear to be disfavored, yet still became more frequent in the viral population.