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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection
PLoS Pathogens, Volume 5, No. 9, Article e1000598, Year 2009
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Description
We previously showed that HIV-1 subtype C viruses elicit potent but highly type-specific neutralizing antibodies (nAb) within the first year of infection. In order to determine the specificity and evolution of these autologous nAbs, we examined neutralization escape in four individuals whose responses against the earliest envelope differed in magnitude and potency. Neutralization escape occurred in all participants, with later viruses showing decreased sensitivity to contemporaneous sera, although they retained sensitivity to new nAb responses. Early nAb responses were very restricted, occurring sequentially and targeting only two regions of the envelope. In V1V2, limited amino acid changes often involving indels or glycans, mediated partial or complete escape, with nAbs targeting the V1V2 region directly in 2 cases. The alpha-2 helix of C3 was also a nAb target, with neutralization escape associated with changes to positively charged residues. In one individual, relatively high titers of anti-C3 nAbs were required to drive genetic escape, taking up to 7 weeks for the resistant variant to predominate. Thereafter titers waned but were still measurable. Development of this single anti-C3 nAb specificity was associated with a 7-fold drop in HIV-1 viral load and a 4-fold rebound as the escape mutation emerged. Overall, our data suggest the development of a very limited number of neutralizing antibody specificities during the early stages of HIV-1 subtype C infection, with temporal fluctuations in specificities as escape occurs. While the mechanism of neutralization escape appears to vary between individuals, the involvement of limited regions suggests there might be common vulnerabilities in the HIV-1 subtype C transmitted envelope. © 2009 Moore et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2742164/bin/ppat.1000598.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2742164/bin/ppat.1000598.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2742164/bin/ppat.1000598.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC2742164/bin/ppat.1000598.s004.tif
Authors & Co-Authors
Moore, Penny L.
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Ranchobe, Nthabeleng
South Africa, Johannesburg
National Institute for Communicable Diseases
Lambson, Bronwen E.
South Africa, Johannesburg
National Institute for Communicable Diseases
Gray, Elin Solomonovna
South Africa, Johannesburg
National Institute for Communicable Diseases
Cave, Eleanor M.
South Africa, Johannesburg
National Institute for Communicable Diseases
Rose-Abrahams, Melissa
South Africa, Cape Town
University of Cape Town
Bandawe, Gama P.
South Africa, Cape Town
University of Cape Town
Mlisana, Koleka P.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Abdool Karim, Salim S.
South Africa, Congella
Centre for the Aids Programme of Research in South Africa
Williamson, Carolyn
South Africa, Cape Town
University of Cape Town
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
South Africa, Johannesburg
University of the Witwatersrand
Statistics
Citations: 239
Authors: 11
Affiliations: 4
Identifiers
Doi:
10.1371/journal.ppat.1000598
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases