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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Analysis of the percentage of human immunodeficiency virus type 1 sequences that are hypermutated and markers of disease progression in a longitudinal cohort, including one individual with a partially defective vif
Journal of Virology, Volume 83, No. 16, Year 2009
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Description
Hypermutation, the introduction of excessive G-to-A substitutions by host proteins in the APOBEC family, can impair replication of the human immunodeficiency virus (HIV). Because hypermutation represents a potential antiviral strategy, it is important to determine whether greater hypermutation is associated with slower disease progression in natural infection. We examined the level of HIV-1 hypermutation among 28 antiretroviral-naive Kenyan women at two times during infection. By examining single-copy gag sequences from proviral DNA, hypermutation was detected in 16 of 28 individuals. Among individuals with any hypermutation, a median of 15% of gag sequences were hypermutated (range, 5 to 43%). However, there was no association between the level of gag hypermutation and the viral load or CD4 count. Thus, we observed no overall relationship between hypermutation and markers of disease progression among individuals with low to moderate levels of hypermutation. In addition, one individual sustained a typical viral load despite having a high level of hypermutation. This individual had 43% of gag sequences hypermutated and harbored a partially defective Vif, which was found to permit hypermutation in a peripheral blood mononuclear cell culture. Overall, our results suggest that a potential antiviral therapy based on hypermutation may need to achieve a substantially higher level of hypermutation than is naturally seen in most individuals to impair virus replication and subsequent disease progression. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2715790/bin/supp_83_16_7805__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2715790/bin/supp_83_16_7805__SupplFig1withLegend.zip
Authors & Co-Authors
Piantadosi, Anne L.
United States, Seattle
Fred Hutchinson Cancer Research Center
United States, Seattle
University of Washington
Humes, Daryl
United States, Seattle
Fred Hutchinson Cancer Research Center
United States, Seattle
University of Washington
Chohan, Bhavna H.
United States, Seattle
Fred Hutchinson Cancer Research Center
United States, Seattle
University of Washington
Kenya, Nairobi
University of Nairobi
McClelland, Raymond Scott
United States, Seattle
University of Washington
Kenya, Nairobi
University of Nairobi
Overbaugh, Julie M.
United States, Seattle
Fred Hutchinson Cancer Research Center
United States, Seattle
University of Washington
Statistics
Citations: 68
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1128/JVI.00280-09
ISSN:
0022538X
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study
Participants Gender
Female