Analysis of human immunodeficiency virus type 1 containing HERV-K protease.
The human endogenous retrovirus, type K (HERV-K) represents the most biologically active form of known retroelements present in the human genome. Several HERV-K genomes have transcriptionally active open reading frames and encode their own protease (PR). The HERV-K PR has been shown to authentically cleave human immunodeficiency virus type 1 (HIV-1) matrix-capsid peptide in the presence of HIV-1 PR inhibitors. This raised the possibility that HERV-K PR could complement HIV-1 PR function in HIV-1-infected individuals. To investigate this possibility, we fused the HIV-1 vpr gene to the HERV-K PR gene (vpr-PR). The vpr-PR expression plasmid and a PR-defective HIV-1 clone were cotransfected into 293T cells. Progeny virions were assayed for processing of the HIV-1 polyproteins by Western blot and for changes in infectivity. HERV-K PR fused to Vpr was incorporated into HIV-1 virions at a high concentration and cleaved the Gag and Pol precursor proteins. However, neither Gag nor Pol polyproteins were correctly processed. Moreover, the HERV-K PR did not restore virus infectivity. While these results do not exclude the possibility that the HERV-K PR could complement an HIV-1 PR whose function is impaired due to drugs or drug-resistant mutations, they clearly demonstrate that the HERV-K PR cannot substitute for the function of the wild-type HIV-1 PR.
Padow
M
M
Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Lai
L
L
Fisher
R J
RJ
Zhou
Y C
YC
Wu
X
X
Kappes
J C
JC
Towler
E M
EM
D002460:Cell Line; D020077:Endogenous Retroviruses / Q000201:enzymology*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015685:Fusion Proteins, gag-pol / Q000378:metabolism*; D016336:Gene Products, vpr / Q000378:metabolism; D016334:Genes, vpr; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids / Q000235:genetics; D011498:Protein Precursors / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015685:Fusion Proteins, gag-pol; D016336:Gene Products, vpr; D011498:Protein Precursors; D011993:Recombinant Fusion Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D010450:Endopeptidases; D016333:HIV Protease