Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

HIV research has made rapid progress and led to remarkable achievements in recent decades, the most important of which are combination antiretroviral therapies (cART). However, in the absence of a vaccine, the pandemic continues, and additional strategies are needed. The 'towards an HIV cure' initiative aims to eradicate HIV or at least bring about a lasting remission of infection during which the host can control viral replication in the absence of cART. Cases of spontaneous and treatment-induced control of infection offer substantial hope. Here, we describe the scientific knowledge that is lacking, and the priorities that have been established for research into a cure. We discuss in detail the immunological lessons that can be learned by studying natural human and animal models of protection and spontaneous control of viraemia or of disease progression. In particular, we describe the insights we have gained into the immune mechanisms of virus control, the impact of early virus-host interactions and why chronic inflammation, a hallmark of HIV infection, is an obstacle to a cure. Finally, we enumerate current interventions aimed towards improving the host immune response.

[Resistance to HIV1 infection in exposed uninfected individuals: light and shadow in the research of mechanisms]. / Résistance au VIH1 chez les individus exposés non infectés : la recherche des mécanismes entre lumière et zones d'ombre.

Some individuals, dubbed here « EU ¼ (exposed but uninfected), do not show any sign of infection in spite of repeated exposures to HIV1. For more than ten years a considerable research effort is made to uncover the mechanisms of resistance to HIV1 in EUs including host factors of protection. Two main not exclusive hypotheses are explored : 1) EUs are resistant to HIV1 infection ought to antiviral innate defences, either genetic or immune ; 2) EUs are protected from infection by immune specific responses that neutralise or eliminate the virus. Various mechanisms have been associated to the resistance to HIV1 infection in studies on different high-risk populations, although none of them can explain all the cases. The resistance to HIV1 infection seems to be linked to the contribution of multiple factors whose relative weight can differ according to EUs ethnic origin, environment and way of exposure.

The pre-transmembrane region of the human immunodeficiency virus type-1 glycoprotein: a novel fusogenic sequence.

We have investigated membrane interactions and perturbations induced by NH(2)-DKWASLWNWFNITNWLWYIK-COOH (HIV(c)), representing the membrane interface-partitioning region that precedes the transmembrane anchor of the human immunodeficiency virus type-1 gp41 fusion protein. The HIV(c) peptide bound with high affinity to electrically neutral vesicles composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and cholesterol (molar ratio, 1:1:1), and induced vesicle leakage and lipid mixing. Infrared spectra suggest that these effects were promoted by membrane-associated peptides adopting an alpha-helical conformation. A sequence representing a defective gp41 phenotype unable to mediate both cell-cell fusion and virus entry, was equally unable to induce vesicle fusion, and adopted a non-helical conformation in the membrane. We conclude that membrane perturbation and adoption of the alpha-helical conformation by this gp41 region might be functionally meaningful.