HIV-1 virions produced from replicating peripheral blood lymphocytes are more infectious than those from nonproliferating macrophages due to higher levels of intravirion reverse transcripts: implications for pathogenesis and transmission.
It has been demonstrated that intravirion reverse transcription in human immunodeficiency virus type I (HIV-1) occurs in the presence of physiological substances and that the intravirion HIV-1 reverse transcripts are important for the establishment of infection in nondividing cells. In this report, we demonstrate that the infectivity of the virus produced from replicating peripheral blood lymphocytes (PBL) is significantly higher than that of virions produced by nonproliferating macrophages, upon infection of either initially quiescent PBLs or macrophages. This directly correlated with significantly higher intravirion reverse transcripts in the virions from replicating PBLs, compared to those from macrophages. Treatment of replicating PBLs and macrophages with 3'- azido-3'- deoxythymidine resulted in decreased intravirion reverse transcripts and lower infectivity of produced virions, upon infection of initially quiescent T-cells or macrophages. Because both nonproliferating macrophages and replicating lymphocytes are the major reservoirs for HIV-1 in vivo, we propose that as the result of higher levels of intravirion reverse transcripts, the HIV-1 virions produced from actively replicating cells are more infectious than those from nonproliferating cells. As such, this scenario implies at least one molecular mechanism for the intra- and interhost transmission of HIV-1.
Dornadula
G
G
Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, Suite 329, Philadelphia, Pennsylvania, 19107, USA.
Zhang
H
H
Shetty
S
S
Pomerantz
R J
RJ
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002453:Cell Cycle; D002460:Cell Line; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D008264:Macrophages / Q000821:virology*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014771:Virion / Q000302:isolation & purification*; D014779:Virus Replication