Particularly, the implication of the C3 region was confirmed by the analysis of diversity using Entropy-One software

Particularly, the implication of the C3 region was confirmed by the analysis of diversity using Entropy-One software. V5 regions. Conclusion This study showed that HIV-1 may continue to evolve in presence of both broadly neutralizing antibodies and increasing autologous neutralizing activity more than 10 years post-infection. Introduction The real impact of the humoral response to the human immunodeficiency virus type 1 (HIV-1) in the course of infection is still a matter PF-915275 of debate [1]C[4]. PF-915275 To date, studies have focused on the neutralizing response since neutralizing antibodies (Nabs) are usually deeply involved in protection against viral infections [5], [6]. In the context of HIV-1 infection, Nabs appear at the early stage of the infection in most of the patients but have been described as ineffective on the long term since they do not seem to be associated with control of viral replication and disease progression [7]. However, Nabs exert a selective pressure on the viral population, leading to continuously evolving viral variants that escape neutralization [8]C[10]. The initial neutralizing antibody response is primarily narrow in its spectrum in most individuals (i.e. autologous neutralization), with heterologous neutralizing antibodies produced in only a fraction of infected individuals later in infection [4], [11], [12]. Several years after primary infection, only a limited percentage of HIV-1 infected patients are able to develop broadly Nabs (bNabs) albeit it appeared that there was a lack of effect of bNabs on disease progression [11], [13], [14]. Some of these patients were characterized as elite neutralizers due the exceptional breadth and potency of their antibodies [15]. A few human broadly neutralizing monoclonal antibodies have been isolated from such patients [16]C[19] and have been shown to be protective in non-human primate studies [20]C[23]. Therefore, the identification of the epitopes targeted by these bNabs, either monoclonal or polyclonal present in human sera, is of prime importance in the perspective of developing an efficient HIV vaccine able to induce protective antibodies [24], [25]. The viral evolution and immune escape experienced by the virus during the acute/early phases of infection have been analyzed in several studies [9], [10], [26]C[30]. These studies have documented the antibody response raised early in infection against the transmitted/founder viruses, the preferentially transmitted variants being considered as those towards which a protective response should be induced by an hypothetical efficient vaccine [31]C[35]. They showed that the pathway that HIV-1 uses to escape the early autologous neutralizing response is not unique, ranging from single amino-acid changes to larger deletions/insertions, and is frequently associated with Rabbit Polyclonal to CAMK5 modification of N-glycosylation sites (PNGS) that led to the concept of an evolving glycan shield at the surface of the envelope spikes [10], [36]. In contrast, little is known about the long-term evolution of the virus in patients who developed bNabs, PF-915275 in particular the mechanism of escape if HIV-1 continues to replicate in presence of these bNabs [37]C[39]. However, this knowledge is crucial for understanding HIV escape to the most efficient Nabs, and might be useful to designing an efficient HIV vaccine. In the present study, we have studied the viral population infecting a long term non progressor (LTNP) HIV-1 infected patient who had developed bNabs at a level compatible with an elite neutralizer status after at least 8 years of infection, over 7 years of follow-up. We provide evidence of PF-915275 continuous evolution of HIV-1 albeit the presence of bNabs, and describe the molecular characteristics of this evolution. Materials and Methods Ethics Statement The institutional review board of Piti Salptrire Hospital (Paris,.