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.

In vivo Infection Dynamics and Human Adaptive Changes of SIVsm-Derived Viral Siblings SIVmac239, SIVB670, and SIVhu in Humanized Mice as a Paralog of HIV-2 Genesis

“…Overall, relative to SIVmac239 and SIVhu, SIV B670 accumulated the largest number of nonsynonymous mutations with corresponding amino acid changes throughout the viral genome (Figure 3B, Table 2). The majority of these changes were found in the 3 ′ end of the viral genome similar to that found in previous studies on SIVsm and SIVcpz in hu-mouse studies (3,37,(48)(49)(50). Interestingly, one of the most striking features amongst the three passaged viruses was the mutation at residue 216 in Gag that appeared within all three different strains of viruses in a highly conserved part of the genome (26,53).…”

“…Both the models permit HIV infection due to the presence of full immune cell repertoire and have been used widely to investigate areas such as HIV pathogenesis, transmission, and latency (33,35,(44)(45)(46)(47). We previously used the hu-mouse model as a human surrogate system to dissect various aspects of the initial crossspecies transmission of SIV chimpanzee virus (SIVcpz) to the human giving rise to HIV-1 and the SIVsm progenitor virus in giving rise to HIV-2 (3,4,39,(48)(49)(50). These studies provided important insights into the important genetic changes these progenitor viruses had to undergo to quickly adapt to the human host and also shed light on the gradual genetic changes that arose as the viruses were serially passaged multiple times using this system.…”

Long‐term evolutionary adaptation of SIVcpz toward HIV‐1 using a humanized mouse model

“…Chimpanzee‐derived SIVs (SIVcpz) are believed to have evolved into the highly pathogenic HIV‐1 Group M 1–3 . An ideal model to recapitulate the genetic adaptations for the cross‐species transmission of SIVcpzLB715 into HIV‐1 Group M is the humanized mouse (hu‐HSC) 4,5 . These hu‐HSC mice harbor a complete functional human immune system permissive for viral infection 4,6–21 .…”

“…Chimpanzee-derived SIVs (SIVcpz) are believed to have evolved into the highly pathogenic HIV-1 Group M. [1][2][3] An ideal model to recapitulate the genetic adaptations for the cross-species transmission of SIVcpzLB715 into HIV-1 Group M is the humanized mouse (hu-HSC). 4,5 These hu-HSC mice harbor a complete functional human immune system permissive for viral infection. 4,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] In this study, we used hu-HSC mice to mimic the selective immune pressures of natural infection by serially passaging SIVcpzLB715 to reproduce the nonsynonymous mutations that resulted in the evolution of HIV-1.…”

Evolution of SIVmac239 following serial passaging in humanized mice

“…SIVmac and its derivatives are widely used as models for HIV infection due to their ability to mimic AIDS‐like pathogenesis in rhesus macaques 1–4 . Previously, we showed successful infection and serial passaging of SIVmac239 as well as other SIVs in the humanized mouse model, which harbors a fully functional human immune system 2–15 . Here, we characterized SIVmac239 following four serial passages in humanized mice and identified the genetic adaptations that arose following in vivo adaptation to the human immune cell environment.…”