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Phenotypic properties of transmitted founder HIV-1.

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Date
2013-04-23
Authors
Parrish, Nicholas F
Gao, Feng
Li, Hui
Giorgi, Elena E
Barbian, Hannah J
Parrish, Erica H
Zajic, Lara
Iyer, Shilpa S
Decker, Julie M
Kumar, Amit
Hora, Bhavna
Berg, Anna
Cai, Fangping
Hopper, Jennifer
Denny, Thomas N
Ding, Haitao
Ochsenbauer, Christina
Kappes, John C
Galimidi, Rachel P
West, Anthony P
Bjorkman, Pamela J
Wilen, Craig B
Doms, Robert W
O'Brien, Meagan
Bhardwaj, Nina
Borrow, Persephone
Haynes, Barton F
Muldoon, Mark
Theiler, James P
Korber, Bette
Shaw, George M
Hahn, Beatrice H
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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.
Type
Journal article
Subject
Base Sequence
CD4-Positive T-Lymphocytes
Cloning, Molecular
Dendritic Cells
Enzyme-Linked Immunosorbent Assay
HIV Infections
HIV-1
Humans
Linear Models
Molecular Sequence Data
Phenotype
Sequence Analysis, DNA
Viral Envelope Proteins
Virion
Permalink
https://hdl.handle.net/10161/14727
Published Version (Please cite this version)
10.1073/pnas.1304288110
Publication Info
Parrish, Nicholas F; Gao, Feng; Li, Hui; Giorgi, Elena E; Barbian, Hannah J; Parrish, Erica H; ... Hahn, Beatrice H (2013). Phenotypic properties of transmitted founder HIV-1. Proc Natl Acad Sci U S A, 110(17). pp. 6626-6633. 10.1073/pnas.1304288110. Retrieved from https://hdl.handle.net/10161/14727.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Denny

Thomas Norton Denny

Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor of Medicine in the Department of Medicine at Duke University Medical Center. He is also an Affiliate Member of the Duke Global Health Institute. Previously, he served on the Health Sector Advisory Council of the Duke University Fuquay School of Business. Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Gao

Feng Gao

Professor Emeritus in Medicine
Dr. Feng Gao is Professor of Medicine at Duke University. The Gao laboratory has a long-standing interest in elucidating the origins and evolution of human and simian inmmunodeficiency viruses (HIV and SIV), and in studying HIV/SIV gene function and pathogenic mechanisms from the evolutionary perspective. These studies have led to new strategies to better understand HIV origins,  biology, pathogenesis and drug resistance, and to design new AIDS vaccines.
Haynes

Barton Ford Haynes

Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology, and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology, and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine Institute, Bart Haynes is leading a team of investigators working on vaccines for emerging infections, including tuberculosis, pandemic influenza, emergi
Alphabetical list of authors with Scholars@Duke profiles.
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