Sensitivity to monoclonal antibody 447-52D and an open env trimer conformation correlate poorly with inhibition of HIV-1 infectivity by SERINC5

Abstract

The host protein SERINC5 inhibits the infectivity of HIV-1 virions in an Env-dependent manner and is counteracted by Nef. The conformation of the Env trimer reportedly correlates with sensitivity to SERINC5.Here, we tested the hypothesis that the "open" conformation of the Env trimer revealed by sensitivity to the V3-loop specific antibody 447-52D directly correlates with sensitivity to SERINC5. Of five Envs tested, SF162 was the most sensitive to neutralization by 447-52D, but it was not the most sensitive to SERINC5; instead the Env of LAI was substantially more sensitive to SERINC5 than all the other Envs. Mutational opening of the trimer by substitution of two tyrosines that mediate interaction between the V2 and V3 loops sensitized the Envs of JRFL and LAI to 447-52D as previously reported, but only BaL was sensitized to SERINC5. These data suggest that trimer "openness" is not sufficient for sensitivity to SERINC5.

Nef enhances HIV-1 replication and infectivity independently of SERINC5 in CEM T cells

“…Modulation of SERINC5 extends to other retroviral proteins, including S2 from equine infectious anemia virus (EIAV) as well as MLV glycoGag ( Rosa et al, 2015 ; Usami et al, 2015 ; Chande et al, 2016 ). HIV-1 Env glycoproteins are differentially sensitive to SERINC-mediated restriction when produced from CD4-negative cells in single-round replication assays; sensitivity correlates to some extent with the degree of Env-trimer openness and instability ( Rosa et al, 2015 ; Usami et al, 2015 ; Beitari et al, 2017 ; Angerstein et al, 2020 ).…”

SERINC5 restricts influenza virus infectivity

“…SERINC5 impairs the infectivity of HIV-1 particles by disrupting viral glycoprotein clusters and hindering viral membrane fusion [6]. Incorporation of SERINC5 into HIV-1 particles also increase HIV-1 susceptibility to the inhibition of neutralization antibodies, suggesting an effect of SERINC5 on the conformation of viral glycoprotein [7,8]. HIV-1 Nef, as well as GlycoGag of murine leukemia virus (MLV) and S2 protein of equine infectious anemia virus (EIAV), counteract SERINC5 by decreasing the expression of SERINC5 at the plasma membrane and excluding it from virions [9][10][11][12].…”