“…Given this diversity, it is not surprising that natural (patient-derived) HIV-1 sequences also exhibit differences in their in vitro function, which may in turn influence viral pathogenesis. For example, it has been hypothesized that HIV-1 subtype C isolates, which comprise more than >50% of infections worldwide (Hemelaar, 2012), may be inherently more transmissible - possibly because of subtype-specific motifs within Env-gp120 that modulate interactions with host cell entry receptors (Walter et al, 2009) - though this remains controversial (Kahle et al, 2014). Subtype-specific differences in HIV-1 entry efficiency (Marozsan et al, 2005), replication capacity (Aralaguppe et al, 2016; Konings et al, 2006), and the function of viral accessory proteins Vif (Binka et al, 2012; Iwabu et al, 2010) and Nef (Mann et al, 2013) have also been described.…”