Dave R, Pomerantz R; Conference on Retroviruses and Opportunistic Infections (11th : 2004 : San Francisco, Calif.).

Program Abstr Conf Retrovir Oppor Infect 11th 2004 San Franc Calif. 2004 Feb 8-11; 11: abstract no. 467.

Ctr. for Human Virology and Biodefense, Thomas Jefferson Univ., Philadelphia, PA, USA

BACKGROUND: The antiviral effect of HIV-1-specific siRNA has been demonstrated by several research groups. However, the targets that were selected in previous studies are not conserved in several neurotropic HIV-1 strains. Previously described studies, including the one we present, will ultimately enable us to evaluate the therapeutic potential of HIV-1-specific siRNA.METHODS: Nine siRNA sequences derived from gp41, nef, tat & rev regions of the viral RNA were assessed for their antiviral effects in this study. Amongst the variety of criteria that were used in selecting these sequences, the most critical one pertained to the fair degree of conservation amongst primary isolates and several neurotropic strains of HIV-1 viz., JR-FL, JR-CSF & YU-2. Synthetic siRNA duplexes were directly transfected into HelaCD4 cells, which were subsequently infected with NL4-3. The antiviral effect of these siRNA was determined by the quantity of p24 antigen secreted into the culture supernatants.RESULTS: The most potent antiviral effect was observed for siRNA derived from gp 41 and nef. In the screening experiments, these siRNA inhibited the infection of HIV-1 NL4-3 to 20.46% [gp41], 20.87% [gp41] & 33.19% [nef] of control at 3dpi. The inhibitory effect intensified with the duration of infection.CONCLUSIONS: These results for the first time demonstrate the potent antiviral effects of gp41-derived siRNA. Of critical significance is the fact that these siRNA sequences are strongly conserved in select neurotropic strains of HIV-1 and fairly well-conserved in several primary isolates. These siRNA can therefore be used as potent antiviral tools for investigations in cells derived from the CNS, to evaluate their therapeutic potential and assess their utility in inhibiting HIV-1 neuropathogenesis and neuroinvasion.

Publication Types:

• Meeting Abstracts

Keywords:

• Antiviral Agents
• Base Sequence
• Gene Products, tat
• Genes, tat
• HIV-1
• RNA, Small Interfering
• RNA, Viral
• genetics
• reverse transcriptase, Human immunodeficiency virus 1

Other ID:

• GWAIDS0031793

UI: 102271430

From Meeting Abstracts