Intravirion display of a peptide corresponding to the dimer structure of protease attenuates HIV-1 replication.
Current treatment of HIV-1-infected individuals involves the administration of several drugs, all of which target either the reverse transcriptase or the protease activity of the virus. Unfortunately, the benefits of such treatments are compromised by the emergence of viruses exhibiting resistance to the drugs. This situation warrants new approaches for interfering with virus replication. Considering the activation of protease in the virus particles, a novel strategy to inhibit HIV-1 replication was tested targeting the dimerization domain of the protease. To test this idea, we have selected four residues from the C terminus of HIV-1 protease that map to the dimer interface region of the enzyme. We have exploited Vpr to display the peptides in the virus particles. The chimeric Vpr exhibited expression and virion incorporation similar to wildtype Vpr. The virus derived from the HIV-1 proviral DNA containing chimeric Vpr sequences registered a reduced level of replication in CEM and CEM X 174 cells in comparison with viruses containing wildtype Vpr. Similar results were observed in a single-round replication assay. These results suggest that the intravirion display of peptides targeting viral proteins is a powerful approach for developing antiviral agents and for dissecting the dynamic interactions between structural proteins during virus assembly and disassembly.
Cartas
M
M
Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Singh
S P
SP
Serio
D
D
Rizvi
T A
TA
Kalyanaraman
V S
VS
Goldsmith
C S
CS
Zaki
S R
SR
Weber
I T
IT
Srinivasan
A
A
D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D016336:Gene Products, vpr / Q000737:chemistry / Q000494:pharmacology*; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D015531:Radioimmunoprecipitation Assay; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D054325:vpr Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D016336:Gene Products, vpr; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D016333:HIV Protease