Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc Natl Acad Sci U S A

Department of Pathology, Veterans Affairs San Diego Healthcare System and the University of California at San Diego, La Jolla, CA 92093-0679, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 05/2003; 100(7):4144-9. DOI: 10.1073/pnas.0630530100
Source: PubMed


A recombinant virus assay was used to characterize in detail neutralizing antibody responses directed at circulating autologous HIV in plasma. Examining serial plasma specimens in a matrix format, most patients with primary HIV infection rapidly generated significant neutralizing antibody responses to early (0-39 months) autologous viruses, whereas responses to laboratory and heterologous primary strains were often lower and delayed. Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations. These data argue that neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection.

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Available from: Christos J Petropoulos, Jan 15, 2015
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    • "The env encoded proteins, gp120 and gp41, are the only HIV-1 proteins that appear on the surface of virions and are responsible for invasion of target cells (Starcich et al., 1986). During HIV infection , successive waves of antibodies target the envelope proteins exerting persistent selection for change (Burton et al., 2005; Richman et al., 2003; Wei et al., 2003). The env gene consequently displays a higher degree of genetic variation than any other HIV genome region. "
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    • "In general, HIV-1-specific NAbs neutralize prior but not contemporary HIV-1 strains in an infected individual (Richman et al. 2003; Wei et al. 2003). Thus, the humoral immune response may not have the capacity to cope with the rapid pace of HIV-1 evolution. "
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    • "In natural infection, the antibodies usually develop within the first few weeks of infection (Moore et al., 1994; Tomaras et al., 2008). However, the antibodies which neutralize autologous viruses were found to be elicited after several weeks of initial infection (Montefiori et al., 2007) and have been demonstrated to exert immune selection pressure on autologous viral variants (Bunnik et al., 2008; Frost et al., 2005; Gray et al., 2007; Li et al., 2006; Richman et al., 2003; Wei et al., 2003). It has been demonstrated earlier that HIV-1 variants that become resistant to autologous neutralizing antibodies in the course of infection by virtue of their escape strategies developed different susceptibilities to monoclonal antibodies and/or heterologous serum or plasma antibodies (Mascola, 2009; Mascola and Montefiori, 2010). "

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