Phenotypic properties of transmitted founder HIV-1.
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 articleSubject
Base SequenceCD4-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
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https://hdl.handle.net/10161/14727Published Version (Please cite this version)
10.1073/pnas.1304288110Publication 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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Show full item recordScholars@Duke
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
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.
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
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