Immunology

Ignition Without Transmission

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Science  30 Jan 2004:
Vol. 303, Issue 5658, pp. 591
DOI: 10.1126/science.303.5658.591b

To ensure optimal replication within its host, the human immunodeficiency virus (HIV) must surmount multiple barriers. One example is the predicament faced by the virus as a result of its need to activate T cells for replication, because activation has the undesired effect of bolstering antiviral immunity.

In their study of the HIV accessory protein Nef, Janardhan et al. show how the virus coopts this adapter protein, which has multiple roles in HIV replication, both in the activation of host T cells and in various forms of immune evasion. Nef was found to associate with and activate the GTPase Rac in T cells. This required association of the Rac-Nef complex with the proteins DOCK2 and ELMO1, and resulted in the impaired responsiveness of activated, Nef-expressing T cells toward chemotactic stimuli. By uniting Rac with its activators, Nef simultaneously facilitates signals that activate HIV-infected cells and those that cripple their capacity to migrate to lymphoid tissues, thus ultimately diminishing the potential for antiviral immunity. — SJS

PLoS Biol. 2, 65 (2004

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