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Phenotypic properties of transmitted founder HIV-1.

dc.contributor.author Barbian, HJ
dc.contributor.author Berg, A
dc.contributor.author Bhardwaj, N
dc.contributor.author Bjorkman, PJ
dc.contributor.author Borrow, P
dc.contributor.author Cai, Fangping
dc.contributor.author Decker, JM
dc.contributor.author Denny, Thomas Norton
dc.contributor.author Ding, Haitao
dc.contributor.author Doms, RW
dc.contributor.author Galimidi, RP
dc.contributor.author Gao, Feng
dc.contributor.author Giorgi, EE
dc.contributor.author Hahn, Beatrice H
dc.contributor.author Haynes, Barton Ford
dc.contributor.author Hopper, J
dc.contributor.author Hora, Bhavna
dc.contributor.author Iyer, SS
dc.contributor.author Kappes, JC
dc.contributor.author Korber, Bette T
dc.contributor.author Li, H
dc.contributor.author Muldoon, M
dc.contributor.author O'Brien, M
dc.contributor.author Ochsenbauer, C
dc.contributor.author Parrish, EH
dc.contributor.author Parrish, NF
dc.contributor.author Shaw, GM
dc.contributor.author Theiler, JP
dc.contributor.author West, AP
dc.contributor.author Wilen, CB
dc.contributor.author Zajic, L
dc.coverage.spatial United States
dc.date.accessioned 2017-06-01T20:32:52Z
dc.date.available 2017-06-01T20:32:52Z
dc.date.issued 2013-04-23
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/23542380
dc.identifier 1304288110
dc.identifier.uri https://hdl.handle.net/10161/14727
dc.description.abstract Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most of these studies were limited to examining envelope (Env) function in the context of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated to higher titers than CC viruses. This difference was significant for subtype B (P = 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic differences of the respective patient cohorts. Together, these data indicate that TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance. These viral properties, which likely act in concert, should be considered in the development and testing of AIDS vaccines.
dc.language eng
dc.relation.ispartof Proc Natl Acad Sci U S A
dc.relation.isversionof 10.1073/pnas.1304288110
dc.subject Base Sequence
dc.subject CD4-Positive T-Lymphocytes
dc.subject Cloning, Molecular
dc.subject Dendritic Cells
dc.subject Enzyme-Linked Immunosorbent Assay
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Linear Models
dc.subject Molecular Sequence Data
dc.subject Phenotype
dc.subject Sequence Analysis, DNA
dc.subject Viral Envelope Proteins
dc.subject Virion
dc.title Phenotypic properties of transmitted founder HIV-1.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/23542380
pubs.begin-page 6626
pubs.end-page 6633
pubs.issue 17
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 110
dc.identifier.eissn 1091-6490


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