Humoral immunity in HIV-1 exposure: cause or effect of HIV resistance?

More than two decades since its discovery, human immunodeficiency virus (HIV) epidemic is still a major burden for health, social and economical reasons on all over the world. Despite the huge effort in basic and applied research, aimed to control virus spread and to design effective therapeutic strategies, an HIV vaccine is not available yet and current therapeutics approaches cannot prevent the infection. To date, both host genetic repertoire, innate and acquired immune responses, viral mutation or attenuation have been invoked to explain the higher or lower individual susceptibility to the infection. The existence of some people somewhat "immune" from infection, despite dealing with repeated HIV exposure, as well as the extremely slow disease progression in some HIV infected individuals, offers valuable clues to elucidate mechanisms underlying natural HIV resistance. Strikingly, both such cohorts, the so-called Exposed Seronegative (ESN, EU, HEPS) and the Slow Progressor (SP, LTNP, LTS) individuals have common immune responses, e.g. the generation of neutralising antibodies directed against common targets, which can play a protective role in virus entry and/or spread. This review focuses on naturally occurring humoral responses to HIV exposure/infection. Moreover, whether such antibodies are induced in response to a peculiar scenario of HIV infection or are generated in the context of an individual innate mode to clear virus infection is a puzzling question, which will be addressed here. The comprehension of mechanisms of natural resistance to HIV infection may have implications for the identification of anti-viral novel strategies and in particular for the development of innovative diagnostics, therapeutics and vaccine design.