Anti-HIV agent MAP30 modulates the expression profile of viral and cellular genes for proliferation and apoptosis in AIDS-related lymphoma cells infected with Kaposi's sarcoma-associated virus

The anti-HIV agent MAP30 (Momordica anti-HIV protein, 30 kDa) inhibits the proliferation of BC-2, an AIDS-related primary effusion lymphoma (PEL) cell line derived from an AIDS patient. BC-2 cells are latently infected with K aposi's sarcoma-associated herpes virus (KSHV), also known as human herpes virus 8 (HHV8). We examined the effect of MAP30 on the expression of viral and cellular genes in BC-2 during latent and lytic states of the viral life cycle. By Northern analysis and RT-PCR, we found that MAP30 downregulates the expression of viral cyclin D (vCD), viral interleukin-6 (vIL-6), and vi ral FLIP (vFLIP), genes involved in cell cycle regulation, viral pathogenes is, and apoptosis. By pathway-specific cDNA microarray analysis, we found t hat BC-2 cells express high levels of egr-1, ATF-2, hsp27, hsp90, I kappaB, mdm2, skp1, and IL-2, cellular genes involved in mitogenesis, tumorigenesi s, and inhibition of apoptosis in NF kappaB and p53 signaling pathways. The se results define for the first time the specific cellular pathways involve d in AIDS-related tumorigenesis and suggest specific novel targets for the treatment. Furthermore, we found that MAP30 downregulates the expression of egr-1, ATF-2, hsp27, hsp90, I kappaB, mdm2, and Skp1, while it upregulates the pro-apoptotic-related genes Bax, CRADD, and caspase-3. Thus, MAP30 mod ulates the expression of both viral and cellular genes involved in KS patho genesis. These results provide valuable insight into the molecular mechanis ms of MAP30 anti-KS action and suggest its utility as a therapeutic agent a gainst AIDS-related tumors. (C) 2001 Academic Press.