How does the humoral response to HIV-2 infection differ from HIV-1 and can this explain the distinct natural history of infection with these two human retroviruses?

A substantial proportion of people infected with HIV-2, the second causative agent of acquired immune deficiency syndrome (AIDS), behave as long-term non-progressors (LTNP) and are able to control the infection more effectively than most HIV-1-infected patients. A better understanding of the differences in the natural history of HIV-1 and HIV-2 infection, and how these relate to the relative immunogenicity and evolution of the two virus strains, could provide important insights into the mechanisms of protective immunity in HIV infection. One of the most striking differences is that most people infected with HIV-2 generate high titers of broadly neutralizing antibodies, whereas this is relatively uncommon in HIV-1 infection. In this review we compare the underlying structural differences of the envelope (Env) between HIV-1 and HIV-2, and examine how these might affect the antibody responses as well as their impact on Env evolution and control of viral replication.