Domain organization of lentiviral and betaretroviral surface envelope glycoproteins modeled with AlphaFold

The surface envelope glycoproteins of non-primate lentiviruses and
betaretroviruses share sequence similarity with the inner proximal
domain  b-sandwich of the human immunodeficiency virus
type 1 (HIV-1) gp120 glycoprotein that faces the transmembrane
glycoprotein as well as patterns of cysteine and glycosylation site
distribution that points to a similar two-domain organization in at least
some lentiviruses. Here, high reliability models of the surface
glycoproteins obtained with the AlphaFold algorithm are presented for the
gp135 glycoprotein of the small ruminant caprine arthritis-encephalitis
(CAEV) and visna lentiviruses and the betaretroviruses jaagsiekte sheep
retrovirus (JSRV), mouse mammary tumor virus (MMTV) and consensus human
endogenous retrovirus type K (HERV-K). The models confirm and extend the
inner domain structural conservation in these viruses and identify two
outer domains with a putative receptor binding site in the CAEV and visna
virus gp135. The location of that site is consistent with patterns of
sequence conservation and glycosylation site distribution in gp135. In
contrast, a single domain is modeled for the JSRV, MMTV and HERV-K
betaretrovirus envelope proteins that is highly conserved structurally in
the proximal region and structurally diverse in apical regions likely to
interact with cell receptors. The models presented here identify sites in
small ruminant lentivirus and betaretrovirus envelope glycoproteins likely
to be critical for virus entry and virus neutralization by antibodies and
will facilitate their functional and structural characterization.