Human immunodeficiency virus infection: association with altered intracellular levels of cAMP and cGMP in MT-4 cells.

T-cells from human immunodeficiency virus (HIV)-infected patients are characterized by a number of qualitative deficiencies including defective T-cell activation. The latter has previously been shown to be normally regulated by cAMP. In this study the patterns of cAMP and cGMP induction in MT-4 cells following HIV infection were investigated. The MT-4 cells were infected with HIV (strain IIIb) and at selected times postinfection (p.i.), culture supernatants were tested for HIV replication by reverse transcriptase activity or HIV P24 Ag. The cells were also examined for their intracellular levels of cAMP and cGMP by radioimmunoassay. HIV infection was associated with an increase in intracellular levels of cAMP and cGMP. The cAMP was increased 40-fold by Day 8 and cGMP 4-fold by Day 4 Pl. The increase in intracellular levels of the cyclic nucleotides (CN) were virus specific, dependent on virus dosage, genetically conserved among the two fresh patient isolates tested, and were abolished by uv inactivation. An increase in cAMP and cGMP was also observed in other cell lines infected with HIV. The sustained elevation in CN level observed could certainly influence cell activation and HIV replication and may potentially have clinical relevance.