Innate responses can be rapidly activated in response to pathogen exposure or infection, and constitute both the first line of defense against infection and early pathogen spread and an important mechanism for triggering the induction of adaptive responses. Their early effector activity may sometimes eradicate infection, but if pathogen replication proceeds and is predominantly combated by adaptive responses they play important roles in regulating the latter as well as making an ongoing contribution to pathogen control. The early effector and immunomodulatory roles of innate responses suggest that they are likely to exert an important influence on critical events in the earliest stages of HIV-1 infection including the establishment of initial foci of infection at mucosal transmission sites and local virus expansion, dissemination to lymph nodes, further viral amplification and spread and the ensuing acute burst of viral replication, as well as having potential to impact on subsequent levels of ongoing viral replication, immune activation and the rate of disease progression.

There is now increasing evidence to indicate that this is the case. Studies in HIV-exposed seronegative cohorts, subjects who have recently acquired HIV-1 infection, non-human primates and other in vivo and in vitro HIV infection models have helped to elucidate the dynamics of activation of different arms of the innate response over the early course of infection and thereafter, and to dissect their complex roles in protection and pathogenesis at different stages of infection. Although innate responses contribute to control of HIV-1 infection via both direct and indirect mechanisms (e.g. through the antiviral activity of certain type 1 interferon (IFN) stimulated genes, or by dendritic cell (DC)-mediated priming of virus-specific CD8 T cell responses), they also have detrimental effects (e.g. type 1 IFNs also drive immune activation and promote apoptosis of T cells and DCs, and DCs are exploited by HIV as a vehicle for virus transfer to CD4 T cells). Better definition of protective and pathogenic aspects of the innate response in HIV-1 infection will pave the way for development of strategies aiming to deploy protective responses and/or downregulate detrimental responses to enhance HIV control and/or prevent disease progression.

This Research Topic will encompass reviews discussing current perspectives, unresolved controversies and new concepts and hypotheses about the complex ways in which innate responses impact on viral control in HIV-1 infection and how their activity may be modulated for HIV prophylaxis or therapy.

Keywords: HIV-1, innate response, dendritic cell, type 1 interferon, NK cell

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