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The Journal of Immunology, 00, 165: 1755-1761.
Copyright © 00 by The American Association of Immunologists

Infection of CD4+ Memory T Cells by HIV-1 Requires Expression of Phosphodiesterase 41

Yu Sun2,*, Linsong Li3,{dagger}, Fion Lau*, Joseph A. Beavo{dagger} and Edward A. Clark4,*,{ddagger}

* Regional Primate Research Center, {dagger} Department of Pharmacology and Molecular, and {ddagger} Department of Microbiology, Cellular Biology Program, University of Washington, Seattle, WA 98195

Using PCR to monitor HIV-1 RNA genome reverse transcription and nuclear import of preintegration complexes, we found that memory, but not naive, CD4+ T cells could support transport of HIV-1 DNA to nuclei upon TCR/CD3 and IL-2 stimulation. Moreover, memory CD4+ T cells, unlike naive CD4+ T cells, express high levels of phosphodiesterase 4 (PDE4) constitutively. Selective blocking of PDE4 activity inhibited IL-2R expression and thereby led to abolishing HIV-1 DNA nuclear import in memory T cells; however, full-length viral DNA synthesis was not affected. Thus, blocking PDE4 prevents initiation of HIV-1 DNA circle formation in T cells. The fact that PDE4 is expressed constitutively at higher levels in memory vs naive CD4+ T cells may help HIV-1 readily infect memory T cells.




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