{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:04:37Z","timestamp":1790485477069,"version":"4.1.0"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,6,18]]},"abstract":"<jats:p>\n                    Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea and HIV.\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    <jats:italic>,<\/jats:italic>\n                    which causes gonorrhea, is particularly adept at driving HIV-1 expression, but the molecular determinants of this relationship remain undefined.\n                    <jats:italic>N. gonorrhoeae<\/jats:italic>\n                    liberates a soluble factor that potently induces expression from the HIV-1 LTR in coinfected cluster of differentiation 4-positive (CD4\n                    <jats:sup>+<\/jats:sup>\n                    ) T lymphocytes, but this factor is not a previously described innate effector. A genome-wide mutagenesis approach was undertaken to reveal which component(s) of\n                    <jats:italic>N. gonorrhoeae<\/jats:italic>\n                    induce HIV-1 expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T lymphocytes. A mutation in the ADP-heptose biosynthesis gene,\n                    <jats:italic>hldA<\/jats:italic>\n                    <jats:italic>,<\/jats:italic>\n                    rendered the bacteria unable to induce HIV-1 expression. The\n                    <jats:italic>hldA<\/jats:italic>\n                    mutant has a truncated lipooligosaccharide structure, contains lipid A in its outer membrane, and remains bioactive in a TLR4 reporter-based assay but did not induce HIV-1 expression. Mass spectrometry analysis of extensively fractionated\n                    <jats:italic>N. gonorrhoeae-<\/jats:italic>\n                    derived supernatants revealed that the LTR-inducing fraction contained a compound having a mass consistent with heptose-monophosphate (HMP). Heptose is a carbohydrate common in microbes but is absent from the mammalian glycome. Although ADP-heptose biosynthesis is common among Gram-negative bacteria, and heptose is a core component of most lipopolysaccharides,\n                    <jats:italic>N. gonorrhoeae<\/jats:italic>\n                    is peculiar in that it effectively liberates HMP during growth. This\n                    <jats:italic>N. gonorrhoeae-<\/jats:italic>\n                    derived HMP activates CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells to invoke an NF-\u03baB\u2013dependent transcriptional response that drives HIV-1 expression and viral production. Our study thereby shows that heptose is a microbial-specific product that is sensed as an innate immune agonist and unveils the molecular link between\n                    <jats:italic>N. gonorrhoeae<\/jats:italic>\n                    and HIV-1.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1303738110","type":"journal-article","created":{"date-parts":[[2013,6,4]],"date-time":"2013-06-04T01:42:51Z","timestamp":1370310171000},"page":"10234-10239","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":57,"title":["<i>Neisseria gonorrhoeae-<\/i>\n                    derived heptose elicits an innate immune response and drives HIV-1 expression"],"prefix":"10.1073","volume":"110","author":[{"given":"Rebecca J.","family":"Malott","sequence":"first","affiliation":[{"name":"Departments of aMolecular Genetics and"},{"name":"Centre for Understanding and Preventing Infection in Children, Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd O.","family":"Keller","sequence":"additional","affiliation":[{"name":"Child and Family Research Institute, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada V5Z 4H4; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan G.","family":"Gaudet","sequence":"additional","affiliation":[{"name":"Departments of aMolecular Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon E.","family":"McCaw","sequence":"additional","affiliation":[{"name":"Departments of aMolecular Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine C. L.","family":"Lai","sequence":"additional","affiliation":[{"name":"Biochemistry, University of Toronto, Toronto, ON, Canada M5S 1A8;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy N.","family":"Dobson-Belaire","sequence":"additional","affiliation":[{"name":"Departments of aMolecular Genetics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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