Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published April 23, 2013 | Published + Supplemental Material
Journal Article Open

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.

Additional Information

© 2013 National Academy of Sciences. Contributed by Beatrice H. Hahn, March 5, 2013 (sent for review January 29, 2013). Published online before print March 29, 2013. We thank John Moore, Frank Kirchhoff, Paul Sharp, and Stuart Shapiro for helpful discussions; the University of Pennsylvania's Center for AIDS Research (CFAR) Human Immunology, Flow Cytometry, and Viral and Molecular Core facilities for reagents and protocols; and Patricia Crystal for artwork and manuscript preparation. This work was supported by National Institutes of Health (NIH) Grants R01 AI45378, R01 AI04088, P30 AI45008, and P30 AI27767, Center for HIV/AIDS Vaccine Immunology Grant U19 AI067854, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant UM1 AI100645, and Bill and Melinda Gates Foundation Grant 37874. N.F.P., S.S.I., and C.B.W. were supported by NIH Training Grant T32 AI07632. Author contributions: N.F.P., F.G., H.L., H.J.B., E.H.P., L.Z., S.S.I., J.M.D., A.K., B.H., A.B., F.C., J.H., T.N.D., H.D., C.O., J.C.K., and C.B.W. performed research; E.E.G., R.P.G., A.P.W., P.J.B., M.O., N.B., M.M., J.P.T., and B.K. contributed new reagents/analytic tools; and N.F.P., E.E.G., C.B.W., R.W.D., P.B., B.F.H., B.K., G.M.S., and B.H.H. wrote the paper.

Attached Files

Published - PNAS-2013-Parrish-6626-33.pdf

Supplemental Material - pnas.201304288SI.pdf

Supplemental Material - sfig01.pdf

Supplemental Material - sfig02.pdf

Supplemental Material - sfig03.pdf

Supplemental Material - sfig04.pdf

Supplemental Material - sfig05.pdf

Supplemental Material - sfig06.pdf

Supplemental Material - sfig07.pdf

Files

sfig07.pdf
Files (9.0 MB)
Name Size Download all
md5:5a7225af2c4cb90a57c3054ceed0bd6a
141.0 kB Preview Download
md5:2f51145fe6348a6c4306d0a741858488
818.7 kB Preview Download
md5:2e247b786ee53e2adf8648cc292cdc0f
763.8 kB Preview Download
md5:146dbc40d87aa29d2ac5dc092f51a779
560.6 kB Preview Download
md5:40090f17329da2b9f036a9bfb7682844
113.7 kB Preview Download
md5:5d51d9ce8c86c98be3e854eb28426eae
1.0 MB Preview Download
md5:9bba06b540517c123857c29bc6bb8f65
5.3 MB Preview Download
md5:59a53bb59bec397573bad41e7891ff96
205.1 kB Preview Download
md5:f81e620f463560b3383f14b760429cab
133.8 kB Preview Download

Additional details

Created:
August 22, 2023
Modified:
October 24, 2023