{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:46:39Z","timestamp":1791215199919,"version":"4.1.0"},"reference-count":75,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2007,9,1]],"date-time":"2007-09-01T00:00:00Z","timestamp":1188604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The mechanism of CD4\n            <jats:sup>+<\/jats:sup>\n            T-cell depletion in human immunodeficiency virus type 1 (HIV-1)-infected individuals remains unknown, although mounting evidence suggests that direct viral cytopathicity contributes to this loss. The HIV-1 Vpr accessory protein causes cell death and arrests cells in the G\n            <jats:sub>2<\/jats:sub>\n            \/M phase; however, the molecular mechanism underlying these properties is not clear. Mutation of hydrophobic residues on the surface of its third alpha-helix disrupted Vpr toxicity, G\n            <jats:sub>2<\/jats:sub>\n            \/M arrest induction, nuclear localization, and self-association, implicating this region in multiple Vpr functions. Cytopathicity by virion-delivered mutant Vpr protein correlated with G\n            <jats:sub>2<\/jats:sub>\n            \/M arrest induction but not nuclear localization or self-association. However, infection with whole virus encoding these Vpr mutants did not abrogate HIV-1-induced cell killing. Rather, mutant Vpr proteins that are impaired for G\n            <jats:sub>2<\/jats:sub>\n            \/M block still prevented infected cell proliferation, and this property correlated with the death of infected cells. Chemical agents that inhibit infected cells from entering G\n            <jats:sub>2<\/jats:sub>\n            \/M also did not reduce HIV-1 cytopathicity. Combined, these data implicate Vpr in HIV-1 killing through a mechanism involving inhibiting cell division but not necessarily in G\n            <jats:sub>2<\/jats:sub>\n            \/M. Thus, the hydrophobic region of the third alpha-helix of Vpr is crucial for mediating G\n            <jats:sub>2<\/jats:sub>\n            \/M arrest, nuclear localization, and self-association but dispensable for HIV-1 cytopathicity due to residual cell proliferation blockade mediated by a separate region of the protein.\n          <\/jats:p>","DOI":"10.1128\/jvi.00122-07","type":"journal-article","created":{"date-parts":[[2007,6,7]],"date-time":"2007-06-07T00:25:36Z","timestamp":1181175936000},"page":"8878-8890","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":52,"title":["Vpr Cytopathicity Independent of G\n            <sub>2<\/sub>\n            \/M Cell Cycle Arrest in Human Immunodeficiency Virus Type 1-Infected CD4\n            <sup>+<\/sup>\n            T Cells"],"prefix":"10.1128","volume":"81","author":[{"given":"Diane L.","family":"Bolton","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, 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