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A small revolution has occurred in the field of AIDS research. A number of chemokines, most of which belong to the CC or beta family, were found by us and others to inhibit HIV infection potently and specifically. The mechanism of such inhibition was shown to be at the level of receptor binding, as these chemokines are binding to receptors that mediate HIV infection. Therefore, chemokines effectively block entry of HIV. Although chemokines have a natural function as chemoattractants, it is intriguing to think that in crossing their path with the virus, they constitute the first example of a naturally occurring soluble molecule, other than antibodies, that can specifically prevent infection. Thus, chemokines could play a role in protective immunity against HIV infection together with other classic correlates, such as neutralizing antibodies and cytotoxic T cells, and some clinical studies suggest that this is indeed the case. Here we review and analyze some of the basic and clinical science that led to the elucidation of the role of chemokines and their receptor in protection from HIV infection.

Viral transcripts, particularly those of the regulatory genes (e.g., rev) in lymphocytic cells chronically infected with human immunodeficiency virus type 2, consist of two types, differing in the structure of the leader sequence derived from the 5' long terminal repeat (LTR). Some transcripts undergo a specific splicing event within the 5' LTR, removing an intron consisting of a part of the R region whereas others do not. Because this spliced-out R region is a part of the trans-activation response element (TAR), it could influence trans-activator (Tat)-mediated trans-activation of viral gene expression. Moreover, this part of the R region is predicted to contain a stable secondary structure that could affect the efficiency of translation of the transcripts without this splicing. Thus, the 5' LTR splicing could have important consequences for virus replication, latency, and pathogenicity.