Regulation of MHC class I and class II and of CD4 expression by HIV-TAT

Viral products can modulate the expression of HLA by various mechanisms as part of the pathogen strategy to elude the immune system.HIV-tat protein has been reported to downregulate the expression of HLA class I genes. Here we show that this effect is not reproducible in a series of both T and macrophage cell lines,transfected with 2-exon tat constructs.Interestingly, the expression of the HIV receptor CD4 was drastically reduced in T,but not in macrophage, cell lines.The effect of tat mutants with substitution in cysteine residues 22 and 37, crucial for protein stabilization and transactivation function, was also investigated.These mutants lost the downregulatory capacity on CD4 but acquired a strong downregulating action on HLA class II antigen expression.The degree of class II downregulation correlated with the amount of tat transcripts expressed in the transfectants.The downmodulatory capacity on CD4 suggests that tat may inhibit superinfection of CD4+ infected cells and on the same time may reduce co-stimulation via CD4 of infected cells,thereby reducing viral replication.However,a similar effect on uninfected T cells may reduce their capacity to optimally respond against foreign antigens.Moreover,the class II downmodulating effect of certain tat mutants, particularly in antigen presenting cells, raises some concern for using these mutants as dominant negative regulators of HIV replication for therapeutical purpose.