Do beta-chemokines have clinical relevance in HIV infection?

Abstract

The role of ␤ -chemokines in HIV infection was evaluated. The kinetics of regulated upon activation of normal T cell expressed and secreted, macrophage inflammatory protein-1 ␣ , and macrophage inflammatory protein 1 ␤ production by stimulated T lymphocytes did not differ substantially between HIV-infected (asymptomatic and with AIDS) and uninfected subjects. Maximal production of these ␤ -chemokines by activated peripheral blood cells was higher in the infected individuals than in uninfected individuals, but no significant difference was observed between healthy infected subjects and AIDS patients. Evaluation of the effect of HIV replication on ␤ -chemokine production indicated that acute infection of CD4 ϩ T cells with non-syncytia-inducing (NSI) viruses generally increased ␤ -chemokine production two to eightfold, whereas with SI strains, it led to decreased production. The sensitivity of an individual's virus to ␤ -chemokine-mediated inhibition correlated with the NSI virus phenotype and a healthy clinical state. 50% of the AIDS patients, however, had NSI viruses that were sensitive to ␤ -chemokines. Finally, anti-␤ -chemokine-neutralizing antibodies caused a more rapid release of HIV by CD4 ϩ T cells naturally infected by NSI, but not SI, viruses indicating that endogenously produced chemokines can affect HIV production in culture. These findings suggest that ␤ -chemokines may affect HIV replication when an NSI virus is involved, but provide little evidence that they substantially influence HIV infection and pathogenesis. ( J. Clin. Invest. 1997. 100: 921-930.)

Chemokine immunobiology in HIV-1 pathogenesis

“…For example, the kinetics of induced ␤-chemokine (MIP-1␣, MIP-1␤, RANTES) secretion are no different between HIV-1-infected or -uninfected individuals, at least in in vitro bulk cultures of activated CD4 ϩ or CD8 ϩ T cells [99]. However, the maximal (total) production of these ␤-chemokines was higher in HIV-1-infected than HIV-1-uninfected individuals, although among HIV-1-positive patients, there was no difference between the levels produced by asymptomatic patients versus those with clinical AIDS [99,100]. In fact, several studies have shown no correlation between long-term nonprogression and ␤-chemokine levels either in serum or from cultured PBMCs [101,102].…”

“…Because both CD4 and CD8 cells secrete ␤-chemokines, it may be the local concentration of ␤-chemokines that may be relevant for inhibiting R5 viral entry. It is interesting to note that HIV-1 infection itself modulates ␤-chemokine secretion: HIV-1-infected CD4 ϩ T cells as well as monocyte/macrophage cultures showed a marked elevation in ␤-chemokine production, however, this was only elicited by infection with R5 and not X4 viruses [48,99]. On the other hand, infection of ex vivo cultured human lymphoid tissue by X4 and not R5-viruses up-regulated ␤-chemokine production [104].…”

“…In addition, because ␣-and ␤-chemokines themselves can induce chemotaxis of NK cells and act to enhance NK-mediated cytolysis [142,143], chemokines elaborated at sites of active inflammation or viral replication [48,99] may serve to synergize the suppressive activity of NK cells.…”

The Unexpected Pleiotropic Activities of RANTES

“…The amount of chemokines required for anti-HIV activity appears to be much higher than the physiologic amount generally found in HIV-infected people (11). It is also curious that R5 viruses induce a greater production of ␤-chemokines than do the X4 viruses (22).…”

CCR5 Expression and β-Chemokine Production During Placental Neonatal Monocyte Differentiation

“…Increased levels of ␤-chemokines have been shown to inhibit HIV infection (34). HIV infection induces ␤-chemokine productions (12,35,36), which presumably play a crucial role in recruiting uninfected T cells and monocytes to sites of active viral replication (35). Thus, differential expression of ␤-chemokines may contribute to the observed difference in susceptibility of CM and CMDM to HIV infection.…”