Generation and characterization of SIVagmSab92018ivTF infectious molecular clone and its "HIV-1 like" derivative

Abstract

To summarize my thesis work, I have generated the first replication-competent molecular clone, SIVagm Sab92018ivTF (SIVagm CON) that has not been adapted to growth in cell culture and is non-pathogenic to natural host African green monkeys. To explore viral determinants that differentiate HIV-1 from other non-pathogenic SIVs, I generated "HIV-1 like" derivative of SIVagm CON clone expressing SIVgsn Vpu, which antagonizes AGM tetherin and HIV-1 Nef which is unable to down-modulate TCR-CD3. An in vivo study in AGMs has been initiated. Initial immunological analysis at 60 week post infection show "HIV-1 like" SIVagm Sab92018ivTF virus is capable of establishing persistent infection and induces higher level immune activation in African green monkeys and will therefore serve as valuable tools to identify those viral properties that contribute to disease progression and HIV pathogenesis.