Purpose of review: Several previous models of HIV dissemination implicated dendritic cells as viral conduits to the lymphatics. However, recent macaque transmission and microbicide studies have highlighted a more complex situation.
Recent findings: Resting CD4 lymphocytes are observed to be the major infected population in mucosal tissue after vaginal challenge with SIV. Resting lymphocytes appear to bridge infection over short distances, whereas activated lymphocytes provide long-distance virus dissemination as a result of greater virus amplification. In addition, dendritic cells might be early carriers of virus, transmitting virus to T cells locally and to the lymph nodes, and thus support parallel mechanisms in transmission. Microbicide studies using agents against CCR5 corroborate a model that infection at the mucosa must occur for transmission to be successful. The fast-rate dendritic cell trafficking of virus to the lymphatics may not result in immediate and efficient viral replication in lymphatic tissue. As dendritic cells might also be infected at the mucosa before lymphatic trafficking, this would enable them to transfer virus in this region at a later timepoint.
Summary: There are now several models that can be attributed to the mucosal acquisition of SIV/HIV. One feature that unites these models is that infection in the mucosa must occur for dissemination to take place. Whether this is a feature of CD4 lymphocytes, dendritic cells or macrophage infection is still unclear. A model that intertwines one or more of the above cell types would be more prudent than addressing each in isolation.
Center for Biomedical Research, Population Council, New York, New York, USA
Correspondence to Stuart Turville, PhD, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10021, USA Tel: +1 212 327 7795; fax: +1 212 327 7764; e-mail: email@example.com
Sponsorship: The Pope laboratory is supported by National Institutes of Health grants R01 AI040877, DE015512 and DE016526, P01 HD041752, U19 AI065413 and R21 AI060405 and DE016534. Support was also provided by the Elizabeth Glaser Pediatric AIDS Foundation and M.P. is an Elizabeth Glaser scientist. Additional support has been provided by the TNPRC base grant RR00164. This publication was also made possible through support provided by the Office of Population and Reproductive Health, Bureau for Global Health, US Agency for International Development, under the terms of award no. HRN-A-00-99-00010. S.G.T. is supported by a C.J. Martin fellowship from the National Health and Medical Research Council of Australia.