Evolutionary rate shifts suggest species-specific adaptation events in HIV-1 and SIV

Maoz Gelbart; Adi Stern

[46]. 185 Env adaptations. Another major barrier for host jumps lies at the cell entry level. CD4 is 186 the target receptor of SIV and HIV, while CCR5 or CXCR4 act as co-receptors, recognized by the 187 viral Env protein which is exposed to the virus external surface. Previous studies mapped the 188 genetic diversity between different chimpanzees' CD4 and revealed that there are several 189 differences between chimpanzee subspecies as well as differences between chimpanzee versus 190 gorilla and human, especially in the regions that are in close contact with Env subunit gp120 [50, 191 51 ]. Some of those changes affect the glycosylation patterns of CD4, making these differences 192 even more distinguishable [50, 51] . It is therefore likely that HIV-1 had to adapt to recognize 193 these differences in CD4. 194 Our analysis overall supports a high level of deceleration and acceleration events found 195 in Env, possibly reflecting the changes that occurred in the host CD4. For instance, many of the 196 changes in M-Env occurred in CD4 interacting residues of Env374, Env455, Env456 and Env458 [52] . 197 However, we cannot rule out that the very high rate of evolution in Env, driven by the adaptive 198 immune system [53] , have led to changes that "mimic" a rate shift. Indeed when accounting for 199 the size of the Env protein, it seems that this protein is less pronounced in its rate shift 200 distribution (Table 1) . 201 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https: //doi.org/10.1101/190769 doi: bioRxiv preprint Gag30 human adaptation marker. Position 30 of Gag polyprotein has been previously 202 suggested to be an adaptation event of HIV-1 to its human host, as it diversified from 203 Methionine in SIVcpzptt and SIVgor strains into Lysine or Arginine in many HIV-1 strains [54] . 204