Derdeyn and E. HIV-1 production was being scored in these experiments, and that computer virus amplification was enhanced by the presence of escort membranes. As a composite, these experiments proved that transinfection can be supported by a variety of escort cells, that cell viability is not required, and that the mechanism is usually susceptible to inhibition by neutralizing antibodies. Apparently, the sophisticated process of DC-SIGN-mediated computer virus internalization and transfer to a T cell synapse3 defines just one of several mechanisms by which an escort can enhance HIV-1 infections.2 Our results support those of Cavrois em et al. /em 2,17 demonstrating that internalization of HIV-1 is not required. CZC-8004 We find that not only can damaged cells support transinfection, but that isolated membranes/microsomes (from uninfected cells) can serve as potent escorts. What are the mechanisms of transinfection in the context of damaged cells or isolated cell membranes? While the details remain to be elucidated, it is likely that membrane fragments bearing appropriate molecules (e.g., DC-SIGN, gp340) bind computer virus and enhance its capacity for capture RGS9 (either by fusion or endocytosis) at the host cell surface. The mere presentation of computer virus on a particulate structure may be sufficient to potentiate this activity. Perhaps lysed cells CZC-8004 are in some cases better escorts than their live cell counterparts, because cell lysis exposes HIV-1 to a labyrinth of internal membranes/microsomes that supplements the plasma cell membrane in computer virus capture and transfer. Cell lysis may additionally alter the cytokine milieu, which could upregulate computer virus production by its target T cell.18 Future experiments designed to define the precise mechanisms of membrane-mediated transinfection are clearly warranted. The fact that fractionated membranes/microsomes support transinfection may help to explain, at least in part, the association of tissue damage with HIV-1 contamination in humans. Clinical trials have shown that persons with injured mucosal tissues are prone to infections with HIV-1.18C21 This association has been proposed to reflect (1) intimate contact of HIV-1 with activated T cell targets and (2) exacerbation of HIV-1 infection by cytokine release. Another explanation that can now be considered is usually that HIV-1 may hijack lifeless and fragmented cells in wounded tissues to enhance computer virus interactions with susceptible T cell targets. Acknowledgments This work was funded by NIH Malignancy Center Support Core Grant P30-CA21765, NIH NIAID-P01 AI45142, NIH NIAID-R01 AI078819, and the American Lebanese Syrian Associated Charities. We thank P. Freiden for helpful technical assistance and S. Naron for assistance with scientific editing. We thank R.V. Srinivas and the AIDS Research and Reference Reagent Program (NRRRP), Division of AIDS, NIAID, NIH, for HIV1IIIB (Contributor R. Gallo). We also thank NRRRP for HIV-1SF2 (Contributor J. Levy), constructs for the production of pseudotyped HIV-1ZM53M (ZM53M.PB12, SVPC11, Contributors C.A. Derdeyn and E. Hunter and pSG3?env plasmids, Contributors J.C. Kappes and X. Wu), TZM-bl cells (Contributors J.C. Kappes, X. Wu, and Tranzyme Inc), MT-2 cells (Contributor D. Richman), and CEM-NKR-CCR5-Luc cells (Contributors J. Moore and C. Spenlehauer). We thank Harold Stamey of the Tennessee Blood Services (Memphis, TN) for human blood samples. Disclosure Statement CZC-8004 No competing financial interests exist..