Interferon-induced alteration of cellular factors affecting HIV alternative splicing, nuclear mRNA export and LTR transcription

Project Member

Dr. Marek Widera

Project Leader

Dr. Marek Widera

Phone: +49 69 6301 – 86102
Fax: +49 69 6301 – 6477
Marek.Widera@kgu.de

Insti­tut für Medi­zinis­che Virolo­gie
Uni­ver­sität­sklinikum Frank­furt
Paul-Ehrlich-Str.40 /​ Haus 41
60590 Frank­furt am Main
Ger­many

Project Summary

The human immun­od­e­fi­cien­cy virus type 1 (HIV‑1) is char­ac­ter­ized by a rel­a­tive­ly small genome. It con­tains numer­ous cis-reg­u­la­to­ry ele­ments that enable pre­cise reg­u­la­tion of the viral gene prod­ucts. Since viral gene expres­sion is depen­dent on the cel­lu­lar machin­ery, effi­cient amounts of cel­lu­lar reg­u­la­to­ry pro­teins (so-called viral depen­den­cy fac­tors) are of cru­cial impor­tance for effi­cient virus repli­ca­tion. Among them, cel­lu­lar RNA-bind­ing pro­teins play a key role in HIV‑1 mRNA pro­cess­ing.
Inter­fer­ons (IFNs) play an impor­tant role in innate immune defense against HIV‑1. They induce the tran­scrip­tion of IFN-stim­u­lat­ed genes (ISG) such as direct antivi­ral restric­tion fac­tors, which cre­ate an antivi­ral state in the host cell. We have recent­ly been able to show that after treat­ment with the clin­i­cal­ly used IFNα2, the expres­sion lev­els of cer­tain RNA bind­ing depen­den­cy fac­tors are down-reg­u­lat­ed in T cells and macrophages. There­fore, with­in the SPP1923 we inves­ti­gate how inter­fer­ons influ­ence viral RNA pro­cess­ing and thus replica­tive capac­i­ty by remov­ing impor­tant play­ers of the viral repli­ca­tion cycle.