Characterization of the behavior of functional viral genomes during the early steps of human immunodeficiency virus type 1 infection.
Infectious viral DNA constitutes only a small fraction of the total viral DNA produced during retroviral infection, and as such its exact behavior is largely unknown. In the present study, we characterized in detail functional viral DNA produced during the early steps of human immunodeficiency virus type 1 infection by analyzing systematically their kinetics of synthesis and integration in different target cells. In addition, we have compared the functional stability of viral nucleoprotein complexes arrested at their pre-reverse transcription state, and we have attempted to measure the kinetics of loss of capsid proteins from viral complexes through the susceptibility of the early phases of infection to cyclosporine, a known inhibitor of the interaction between viral capsid and cyclophilin A. Overall, our data suggest a model in which loss of capsid proteins from viral complexes and reverse transcription occur concomitantly and in which the susceptibility of target cells to infection results from a competition between the ability of the cellular environment to quickly destabilize viral nucleoprotein complexes and the capability of the virus to escape such targeting by engaging the reverse transcription reaction.
Arfi
Vanessa
V
LaboRetro, Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France.
Lienard
Julia
J
Nguyen
Xuan-Nhi
XN
Berger
Gregory
G
Rigal
Dominique
D
Darlix
Jean-Luc
JL
Cimarelli
Andrea
A
D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D016679:Genome, Viral; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D048348:Reverse Transcription; D019065:Virus Assembly; D016662:Virus Integration; D014779:Virus Replication
D036022:Capsid Proteins; D004279:DNA, Viral