Abstract
T cells actively migrate along reticular networks within lymphoid organs in search for cognate antigen, but how these behaviors impact HIV entry and infection is unclear. Here, we show that migratory T cells in 3D collagen matrix display significantly enhanced infection and integration by cell-free R5-tropic lab adapted and transmitted/founder molecular HIV clones in the absence of exogenous cytokines or cationic polymers. Using two different collagen matrices that either support or restrict T cell migration, we observe high levels of HIV fusion in migratory T cells, whereas non-motile T cells display low viral entry and integration. Motile T cells were less sensitive to combination antiretroviral drugs and were able to freely migrate into regions with high HIV densities, resulting in high infection rates. Together, our studies indicate that the environmental context in which initial HIV-T cell encounters occur modulates HIV-1 entry and integration efficiencies.
| Original language | English (US) |
|---|---|
| Article number | 110406 |
| Journal | Cell reports |
| Volume | 38 |
| Issue number | 8 |
| DOIs | |
| State | Published - Feb 22 2022 |
Bibliographical note
Funding Information:We would like to thank Dr. Christine Zhang from the Flow core facility at the University of Manitoba. We thank Dr. Eric Cohen for sharing the pCMV4-BlaM-Vpr plasmid. Cells, ART drugs, and viruses were received from the National Institute of Health HIV Reagent Program. This work was supported in part by the Canadian Institutes of Health Research (CIHR) Project grant ( PJT 155951 ), the CanCure Enterprise ( HIG-133050 ), and Research Manitoba (T.T.M.). This work was supported in part by internal funds of the Department of Medicine at the University of Minnesota to A.H.
Funding Information:
We would like to thank Dr. Christine Zhang from the Flow core facility at the University of Manitoba. We thank Dr. Eric Cohen for sharing the pCMV4-BlaM-Vpr plasmid. Cells, ART drugs, and viruses were received from the National Institute of Health HIV Reagent Program. This work was supported in part by the Canadian Institutes of Health Research (CIHR) Project grant (PJT 155951), the CanCure Enterprise (HIG-133050), and Research Manitoba (T.T.M.). This work was supported in part by internal funds of the Department of Medicine at the University of Minnesota to A.H. P.L. N.C. and T.T.M. conceived and designed the experiments; P.L. O.A. A.P. W.H.K. and R.Z. performed the experiments; A.H. provided critical plasmids; P.L. A.P. R.Z. N.C. and T.T.M. analyzed the data; P.L. and T.T.M. wrote the manuscript. The authors declare no competing financial interests.
Publisher Copyright:
© 2022 The Author(s)
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
