Fluorescent image analysis of HIV-1 and HIV-2 uncoating kinetics in the presence of old world monkey TRIM5?.

ABSTRACT: Uncoating of Human Immunodeficiency Virus type 1 (HIV-1) and type 2 (HIV-2) conical cores is an important early step for establishment of infection. In Old World Monkey (OWM) cells, the TRIM5? cellular factor potently suppresses an early step of infection by HIV-1. Previously, biochemical studies using whole cell lysates of infected cells revealed that OWM TRIM5? accelerates the uncoating of HIV-1, leading to premature reverse transcription. In the present study, we re-evaluated uncoating kinetics of HIV-1 in the presence of OWM TRIM5? by using an in situ uncoating assay, which allowed us to differentiate productive HIV-1 entry from simple (non-productive) endocytosis. Results showed that the uncoating kinetics of HIV-1 was indeed accelerated in the presence of OWM TRIM5?. Furthermore, we adapted an in situ uncoating assay to HIV-2, which showed wide variations in TRIM5? sensitivity among different isolates. HIV-2 isolate GH123, whose infectivity was suppressed by cynomolgus monkey (CM) TRIM5?, showed accelerated uncoating in the presence of CM TRIM5?. In contrast, mutant HIV-2 ASA, whose infectivity was unaltered by CM TRIM5?, showed no change in uncoating kinetics in the presence of CM TRIM5?. These results confirmed and further extended the previous notion that accelerated uncoating is associated with restriction activity of TRIM5? against lentiviruses.

SUBMITTER: Takeda E 

PROVIDER: S-EPMC4372348 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature