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.

Download full-text


Available from: Christos J Petropoulos, Jan 15, 2015
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 group M (HIV-1M) epidemic in central/west Africa. Here, we analysed new subtype G env sequences sampled from 8 individuals in Yaoundé, Cameroon during 2007-2010, together with all publically available subtype G-attributed full-length env sequences with known sampling dates and locations. We inferred that the most recent common ancestor (MRCA) of the analysed subtype G env sequences most likely occurred in ∼1953 (95% Highest Posterior Density interval (HPD) 1939-1963): about 15years earlier than previous estimates. We found that the subtype G env phylogeny has a complex structure including seven distinct lineages, each likely dating back to the late 1960s or early 1970s. Sequences from Angola, Gabon and the Democratic Republic of Congo failed to group consistently in these lineages, possibly because they are related to more ancient sequences that are poorly sampled. The circulating recombinant form (CRF), CRF06_cpx env sequences but not CRF25_cpx env sequences are phylogenetically nested within the subtype G clade. This confirms that the CRF06_cpx env plausibly was derived through recombination from a subtype G parent, and suggests that the CRF25_cpx env was likely derived from an HIV-1M lineage related to the MRCA of subtype G that has remained undiscovered and may be extinct. Overall, this fills important gaps in our knowledge of the early events in the spread of HIV-1M. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: B cell functional defects are associated with delayed neutralizing antibody development in pathogenic lentivirus infections. However, the timeframe for alterations in the antibody repertoire and somatic hypermutation (SHM) remains unclear. Here, we utilized the SIV/rhesus macaque (RM) model to investigate the dynamics of immunoglobulin VH gene diversity and SHM following infection. Three RMs were infected with SIVmac239, and VH1, VH3, and VH4 genes were amplified from peripheral blood at 0, 2, 6, 24, and 36 weeks postinfection for next-generation sequencing. Analysis of over 3.8 million sequences against currently available RM germline VH genes revealed a highly biased VH gene repertoire in outbred RMs. SIV infection did not significantly perturb the predominant IgG1 response, but overall immunoglobulin SHM declined during the course of SIV infection. Moreover, SHM at the AID deamination hotspot, WRC, rapidly decreased and was suppressed throughout SIV infection. In contrast, a transient increase in mutations at the APOBEC3G deamination hotspot, CCC, coincided with a spike in APOBEC3G expression during acute SIV infection. The results outline a timetable for altered VH gene repertoire and IgG SHM in the SIV/RM model and suggest a burst of APOBEC3G-mediated antibody SHM during acute SIV infection.
    Full-text · Article · May 2015 · Immunogenetics
  • Source
    • "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). "

    Full-text · Conference Paper · Oct 2014
Show more