Phenotypic properties of transmitted founder HIV-1

Parrish, Nicholas F and Gao, Feng and Li, Hui and Giorgi, Elena E and Barbian, Hannah J and Parrish, Erica H and Zajic, Lara and Iyer, Shilpa S and Decker, Julie M and Kumar, Amit and Hora, Bhavna and Berg, Anna and Cai, Fangping and Hopper, Jennifer and Denny, Thomas N and Ding, Hairao and Ochsenbauer, Christina and Kappes, John C and Galimidi, Rachel P and West, Anthony P Jr and Bjorkman, Pamela J and Wilen, Craig B and Doms, Robert W and O'Brien, Meagan and Bhardwaj, Nina and Borrow, Persephone and Haynes, Barton F and Muldoon, Mark and Theiler, James P and Korber, Bette and Shaw, George M and Hahn, Beatrice H (2013) Phenotypic properties of transmitted founder HIV-1. PNAS, 110 (17). pp. 6626-6633. ISSN 1091-6490

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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.

Item Type:	Article
Uncontrolled Keywords:	HIV-1, HIV-1 viral dynamics, HIV transmission, acute HIV infection
Subjects:	MSC 2010, the AMS's Mathematics Subject Classification > 92 Biology and other natural sciences
Depositing User:	Dr Mark Muldoon
Date Deposited:	15 May 2013
Last Modified:	20 Oct 2017 14:13
URI:	https://eprints.maths.manchester.ac.uk/id/eprint/1977

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