A3G Complexes: A Novel Role of A3G in Restricting the Late Steps of HIV-1 Replication

Abstract

APOBEC3G (A3G) is a cytidine deaminase that inhibits the replication of human immunodeficiency virus type 1 (HIV-1) in the absence of the HIV-1 virion infectivity factor (Vif) protein. However, in the presence of the viral Vif protein, A3G is targeted for proteasomal degradation. If not degraded, A3G is packaged into progeny virions where it inhibits early steps of HIV-1 replication in the target cell. This work identifies and characterizes the ability of A3G to restrict late steps of HIV-1 replication in the producer cell. A3G is found in two forms in cells: in a diffuse Low Molecular Mass (LMM) form and a large High Molecular Mass (HMM) form. We call the HMM form “A3G Complexes”. We show that A3G complexes partially co-localize with RNA granules and decrease HIV-1 production. This restriction of virus production exists only when A3G is found within complexes. A3G complexes shorten the half-life of an intracellularly-retained Gag protein. Different late HIV-1 replication steps are restricted by RNA granules that contain A3G versus those without A3G. This work will lead to better understanding of the biology of A3G complexes and RNA granules as they relate to HIV-1 replication.