Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects

Canducci, Filippo; Marinozzi, Maria Chiara; Sampaolo, Michela; Berrè, Stefano; Bagnarelli, Patrizia; Degano, Massimo; Gallotta, Giulia; Mazzi, Benedetta; Lemey, Philippe; Burioni, Roberto; Clementi, Massimo

doi:10.1186/1742-4690-6-4

Cited by 18 publications

(18 citation statements)

References 64 publications

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“…Not surprisingly, codons under diversifying selection (positive selection) seem to be clustered mostly in the hypervariable V1/V2 and V3 regions that contain important and accessible neutralizing targets [49], [50]. The impact of the neutralizing antibody response in the in vivo evolution of the HIV-2 Env is currently unknown.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection

Barroso

Borrego²,

Bártolo

et al. 2011

PLoS ONE

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BackgroundUnlike in HIV-1 infection, the majority of HIV-2 patients produce broadly reactive neutralizing antibodies, control viral replication and survive as elite controllers. The identification of the molecular, structural and evolutionary footprints underlying these very distinct immunological and clinical outcomes may lead to the development of new strategies for the prevention and treatment of HIV infection.Methodology/Principal FindingsWe performed a side-by-side molecular, evolutionary and structural comparison of the C2, V3 and C3 envelope regions from HIV-1 and HIV-2. These regions contain major antigenic targets and are important for receptor binding. In HIV-2, these regions also have immune modulatory properties. We found that these regions are significantly more variable in HIV-1 than in HIV-2. Within each virus, C3 is the most entropic region followed by either C2 (HIV-2) or V3 (HIV-1). The C3 region is well exposed in the HIV-2 envelope and is under strong diversifying selection suggesting that, like in HIV-1, it may harbour neutralizing epitopes. Notably, however, extreme diversification of C2 and C3 seems to be deleterious for HIV-2 and prevent its transmission. Computer modelling simulations showed that in HIV-2 the V3 loop is much less exposed than C2 and C3 and has a retractile conformation due to a physical interaction with both C2 and C3. The concealed and conserved nature of V3 in the HIV-2 is consistent with its lack of immunodominancy in vivo and with its role in preventing immune activation. In contrast, HIV-1 had an extended and accessible V3 loop that is consistent with its immunodominant and neutralizing nature.Conclusions/SignificanceWe identify significant structural and functional constrains to the diversification and evolution of C2, V3 and C3 in the HIV-2 envelope but not in HIV-1. These studies highlight fundamental differences in the biology and infection of HIV-1 and HIV-2 and in their mode of interaction with the human immune system and may inform new vaccine and therapeutic interventions against these viruses.

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Section: Introductionmentioning

confidence: 99%

Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection

Barroso

Borrego²,

Bártolo

et al. 2011

PLoS ONE

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“…Earlier, Canducci et al (2009) observed that evolutionary rate of HIV-1 env gene varies between NP and LTNP patients. The evolutionary rate (ω) for the env sequences of RP, SP, and LTNP type was found to correlate significantly with Axis 1 ( R = −0.31, P < 0.01) of RAAU data.…”

Section: Resultsmentioning

confidence: 98%

HIV Progression Depends on Codon and Amino Acid Usage Profile of Envelope Protein and Associated Host-Genetic Influence

2017

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Acquired immune deficiency syndrome (AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV). Two types of HIV have been characterized: HIV-1 and HIV-2. The present study investigated whether evolutionary selection pressure differs between rapid progressor (RP), slow progressor (SP), and long-term non-progressor (LTNP) of HIV-I infected individuals. An unexpected association between the evolutionary rate of substitution in envelope (env) gene and disease progression is observed. Our present study suggests that env genes of LTNP are subject to unusually strong functional constraint with respect to RP. We also observed that the three categories of env genes i.e., RP, SP, and LTNP, had their own characteristic pattern of amino acid usage and SP and LTNP sequences shared similar patterns of amino acid usage different from RP sequences and evolutionary rate significantly influenced the amino acid usage pattern of the three different types of env gene sequences. It was also noted that the evolutionary rate for the glycosylation sites of LTNP and SP sequences were even significantly less than the RP sequences. Comparative analysis on the influence of human host on the three categories of env genes are well correlated with the rates of disease progression suggesting the adaptive strategies of the viruses for successful residence and infection. Host associated selective constraints appeared most relaxed on the RP sequences and strongest in LTNP sequences. The present study clearly portrays how evolutionary selection pressure differs between three categories of env genes i.e., RP, SP, and LTNP. The env genes, coding for the env glycoproteins, experience severe selection constraints from the host due to their constant exposure to the host immune system. In this perspective it might be suggested that env gene evolution occurs mainly by negative selection with the occurrence of mutation that might not reach fixation in the viral population. This work also confers a deeper insight into the crucial effects of host factors that govern the overall progression of HIV infection.

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“…The cocktail strategy may be especially relevant in the case of HIV where cytotoxic T lymphocytes and neutralizing Abs have long been known to select for immune escape mutations during the course of infection [54][55][56][57]. In addition, inactivation of bnAbs by non-nAbs has been reported [58][59][60][61].…”

Section: Introductionmentioning

confidence: 99%

Multiantibody Strategies for HIV

Hiatt

Zeitlin

Whaley

2013

Clinical and Developmental Immunology

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Vaccination strategies depend entirely on the appropriate responsiveness of our immune system against particular antigens. For this active immunization to be truly effective, neutralizing antibodies (nAbs) need to efficiently counter the infectivity or propagation of the pathogen. Some viruses, including HIV, are able to take advantage of this immune response in order to evade nAbs. This review focuses on viral immune evasion strategies that result directly from a robust immune response to infection or vaccination. A rationale for multi-Ab therapy to circumvent this phenomenon is discussed. Progress in the formulation, production, and regulatory approval of monoclonal antibodies (mAbs) is presented.

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Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects

Cited by 18 publications

References 64 publications

Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection

Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection

HIV Progression Depends on Codon and Amino Acid Usage Profile of Envelope Protein and Associated Host-Genetic Influence

Multiantibody Strategies for HIV

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