Phenotypic properties of transmitted founder HIV-1.
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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.
Enzyme-Linked Immunosorbent Assay
Molecular Sequence Data
Sequence Analysis, DNA
Viral Envelope Proteins
Published Version (Please cite this version)10.1073/pnas.1304288110
Publication InfoParrish, 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.
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Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI) and the Center for HIV/AIDS Vaccine Immunology (CHAVI), 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. He has recently been appointed to the Duke University Fuqua School of Business Health Sector Advisory Council. Previously, he was an Associate Professor of Pathology, Laboratory M
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.
Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
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