s Kaposi's sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi's sarcoma (KS) in 1994.KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD).Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons.The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.

HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent, treat and to better understand the disease, it is one of the main causes of morbidity and mortality worldwide. Currently, there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects, price and drug resistance, it is essential to discover new targets, to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.

Objective:To analyze expression and models of CD39,CTLA-4,and PD-1 on T cells,to investigate effect of cyclic adenosine monophosphate(cAMP)on their expressions,and to analyze key pathways regulating their expressions.Methods:Small molecules such as adenylate cyclase(ACs)activators,phosphodiesterase(PDE)inhibitors,protein kinase A(PKA)inhibitors and PKA-CREB inhibitors were used to stimulate rhesus macaque peripheral blood mononuclear cells in vitro,and changes in ratios of CD39,CTLA-4,and PD-1 positive(CD39+,CTLA-4+,and PD-1+)T cells were detected by flow cytometry,and to analyze their expression patterns,and effects of small molecules on ratio of positively expressing/co-expressing cells were compared to clarify expres-sion patterns and molecules and pathways that regulated expression.Results:Normal macaque CD4+T and CD8+T cells had low ratios of CD39+,CTLA-4+,and PD-1+cells,and positive cells predominantly expressed only one of these molecules.Increasing intracellular cAMP levels did not affect CD39+T cell ratio,significantly increased CTLA-4+T cell ratio,and decreased PD-1+CD8+T cell ratio,involving cell populations with mono expression of CTLA-4 and PD-1.Inhibition of PKA activity reduced potentiation of CTLA-4 expression by broad-spectrum PDE inhibitor,3-isobutyl-1-methylxanthine(IBMX),but did not affect PD-1 expression.Exchange protein activated by cAMP did not affect CTLA-4 expression but downregulate PD-1+CD4+/CD8+T cells ratio.Upregulation of CTLA-4 by PDE4B selective inhibitors was similar to IBMX,while regulation of PDE3 and PDE5A selective inhibitors on PD-1 expression was similar to IBMX.Conclusion:CD39,CTLA-4 and PD-1 have different expression models on T cells but are differentially regulated by cAMP levels and have different cAMP downstream signal pathways involved in expression regulation.