Chemokines, cytokines and HIV: a complex network of interactions that influence HIV pathogenesis

The important role of chemokine receptors in HIV pathogenesis is becoming i ncreasingly apparent. The level at which certain chemokine receptors that s erve as HIV co-receptors are available influences the susceptibility of a C D4(+) cell to viral infection and to certain HIV envelope-induced alteratio ns in cellular function. Numerous pathogens, including HIV can stimulate th e production of chemokines and cytokines from a variety of cell types. Both cytokines and chemokines modulate CCR5 and CXCR4 availability, resulting i n differential replication potentials for R5 and X4 HIV strains depending o n the milieu in the microenvironment. In addition, differential expression of CCR5 and CXCR4 on activated memory T cells appears to play an important role in preferential replication of R5 HIV strains in vivo. However, expres sion of HIV co-receptors and CD4 may not be sufficient for effective HIV en try and replication. Intracellular signaling events, triggered by interacti on between chemokine receptors and chemokines or HN envelope, are important for efficient entry and completion of early replication events. Envelope p roteins of different HN isolates vary in their ability to transduce these s ignals, a characteristic that may play a role in determining the ability of a virus to productively infect certain cell types. Finally, the interactio n between chemokine receptors and chemokines or HIV envelope has significan t effects on cellular functions which likely play a role in HIV pathogenesi s.