Marshall WL, Datta R, Hanify K, Teng E, Finberg RW; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 4th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 4th 1997 Wash DC. 1997 Jan 22-26; 4th: 151 (abstract no. 471).
Dana-Farber Cancer Institute, Boston, MA.
HIV infection of monocytic cells is thought to be extremely important in the early stages of HIV infection. We sought to examine the effect of anti-apoptotic gene expression upon HIV replication in monocytic cells. To this end, we transfected U937 with bcl-xl to obtain a clone of U937 promonocytic cells which overexpressed bcl-xl, designated U937bcl-xl, and a negative control U937 clone transfected with vector alone, designated U937neo. Control U937 cells transfected with vector alone undergo apoptosis four times as frequently as the U937bcl-xl cells. Agarose gel electrophoresis demonstrates the presence of internucleosomal fragmentation of DNA in the HIV infected cells: H9, U937neo, and U937bcl-2. Only minimal fragmentation was detected in the U937bcl-xl cells. Furthermore, U937bcl-xl cells produce up to 10-fold less HIV-1 protein than U937neo. A recent report demonstrates that HIV-1 protease cleaves bcl-2, leading to both the apoptotic death of T cells and HIV production. We did not detect significant loss of bcl-xl expression following HIV infection, suggesting that bcl-xl is resistant to proteolytic cleavage by HIV-1MN protease. These results show that HIV replication and apoptosis in monocytic cells in vitro can be inhibited by bcl-xl expression. Therapies that up-regulate bcl-xl expression in monocytes and T cells potentially provide a novel means to decrease the destructiveness and spread of HIV.
Publication Types:
Keywords:
- AIDS Dementia Complex
- Acquired Immunodeficiency Syndrome
- Apoptosis
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- In Vitro
- Monocytes
- T-Lymphocytes
- U937 Cells
Other ID:
UI: 102223291
From Meeting Abstracts