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Abstract
Acquisition of maximal infectivity by HIV-1 virions
Boukrinskaia A.1, Sharkey M.2, Dauphin A.2, Stevenson M.2
Introduction: According to current models, viral maturation and acquisition of infectivity occurs after virions detach from the infected cell membrane. We initiated the current study when we observed that there was a time dependent relationship in the acquisition of maximal infectivity by HIV-1 virions. Thus, virions harvested at early intervals postinfection (18-24 hours post-infection) were approximately one log less infectious than virions harvested 48 hours post-infection when normalized to gag protein content or reverse transcriptase activity. While early and late virions contained similar amount of processed gag proteins, early virions exhibited morphological defects suggesting a requirement for factors in addition to gag precursor cleavage for acquisition of maximal infectivity.
Methods: To evaluate whether early virions could reacquire infectivity after assembly, virus particles were made in the presence of protein inhibitors and then subsequently dialyzed. To determine whether the time-dependent acquisition of infectivity could be normalized by expression of viral proteins prior to infectivity, cells were first transfected with defective HIV-1 molecular clones that express all viral proteins and subsequently infected with wild-type HIV, and time-dependent acquisition of infectivity evaluated.
Results: When virions were manufactured in the presence of protease inhibitors and protease inhibitors subsequently dialyzed, virions harvested 48 hours post-infection reacquired infectivity while those harvested 18-24 hours post-infection did not. In addition, expression of viral proteins prior to infection normalized the infectivity of virions harvested 18 and 24 hours post-infection.
Conclusions: Collectively, these experiments suggest the existence of factors in addition to virion proteins that must be packaged for resulting virions to acquire maximal infectivity. The time-delay in acquisition of maximal infectivity might represent an interval in which de novo viral protein expression induces viral or cellular factors required for maximal virion infectivity.
The 3rd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
MoPe17.2B01
Suggested Citation
"BoukrinskaiaA., et al.
Acquisition of maximal infectivity by HIV-1 virions.
Poster Exhibition:
The 3rd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
MoPe17.2B01"
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