Impaired nuclear import and viral incorporation of Vpr derived from a HIV long-term non-progressor.
We previously reported an epidemiologically linked HIV-1 infected patient cohort in which a long-term non-progressor (LTNP) infected two recipients who then exhibited normal disease progression. Expression of patient-derived vpr sequences from each of the three cohort members in mammalian cells tagged with GFP revealed a significant reduction in Vpr nuclear import and virion incorporation uniquely from the LTNP, whereas Vpr from the two progressing recipients displayed normal localisation and virion incorporation, implying a link between efficient Vpr nuclear import and HIV disease progression. Importantly, an F72L point mutation in the LTNP was identified for the first time as being uniquely responsible for decreased Vpr nuclear import.
Caly
Leon
L
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. leon.caly@med.monash.edu.au
Saksena
Nitin K
NK
Piller
Sabine C
SC
Jans
David A
DA
D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D018450:Disease Progression; D015870:Gene Expression; D016336:Gene Products, vpr / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017354:Point Mutation; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D016336:Gene Products, vpr; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins