Abstract
The genetic evolution of HIV-1 from its progenitor virus SIV following cross-species transmission is not well understood. Here we simulated the SIVcpz initial transmission to humans using humanized mice and followed the viral evolution during serial passages lasting more than a year. All three SIVcpz progenitor viruses used, namely LB715 and MB897 (group M) as well as EK505 (group N) readily infected hu-mice resulting in chronic viremia. Viral loads increased progressively to higher set-points and the CD4+ T cell decline became more pronounced by the end of the second serial passage indicating viral adaptation and increased pathogenicity. Viral genomes sequenced at different time points revealed many non-synonymous variants not previously reported that occurred throughout the viral genome, including the gag, pol, env, and nef genes. These results shed light on the potential changes that the SIVcpz genome had undergone during the initial stages of human infection and subsequent spread.
Highlights
Throughout history, cross-species transmission of animal viruses to humans gave rise to a number of deadly pathogens including HIV-1
Previous data on HIV-1 BaL infections in hu-hematopoietic stem cells (HSC) mice showed that peak viral loads were reached at around 8 weeks post-inoculation (Berges et al, 2010)
This is unlike the first generation of SIVcpz inoculations into hu-HSC mice where SIVcpzEK505, SIVcpzMB897 do not display peak viral loads till days 84 and 119, respectively, and SIVcpzLB715 does not peak during the first generation
Summary
Throughout history, cross-species transmission of animal viruses to humans gave rise to a number of deadly pathogens including HIV-1. While humans and chimpanzees are highly related from an evolutionary and genetic standpoint, they do harbor very divergent and often unique host restriction factors that provide protection from various viral infections including those from NHP lentiviruses (Wain et al, 2007; Sauter and Kirchhoff, 2019). These factors, in combination with differences in host cell receptors such as CD4+ and chemokine receptors, such as CCR5 and CXCR4, pose considerable barriers that SIVs need to overcome to evolve into HIV-1 (Hvilsom et al, 2008; Locatelli and Peeters, 2012). A suitable model system needs to be employed to evaluate the critical questions surrounding the initial events of cross-species transmission and viral evolution during serial human propagation
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