{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:33:37Z","timestamp":1790980417840,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["3P20GM103418-21S1, P20GM130448, R01GM147542, 5R21AI173784-02"],"award-info":[{"award-number":["3P20GM103418-21S1, P20GM130448, R01GM147542, 5R21AI173784-02"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2026,3,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Beta human papillomaviruses (\u03b2-HPVs) are ubiquitous double-stranded DNA (dsDNA) viruses that may promote skin cancers by destabilizing the host genome. Supporting this, expression of the E6 gene from a \u03b2-HPV (\u03b2-HPV 8 E6) results in increased micronuclei that should induce an innate immune response that eliminates these cells. However, \u03b2-HPV 8 E6 promotes rather than restricts proliferation. We hypothesize that \u03b2-HPV 8 E6 accomplishes this by attenuating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, an innate immune pathway that becomes activated in response to cytosolic dsDNA. Here, we show that in response to dsDNA transfection, \u03b2-HPV 8 E6 reduced the intensity of cGAS-STING pathway activation via a reduction in STING phosphorylation. Additionally, our unbiased assessment found that \u03b2-HPV 8 E6 broadly downregulates innate immunity. This impairment of the cGAS-STING innate immune response could contribute to the prevalence of \u03b2-HPV infections.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Beta human papillomaviruses (\u03b2-HPVs) may promote non-melanoma skin cancers in certain immunocompromised populations by destabilizing the host genome. Our group has previously documented the ability of a specific \u03b2-HPV, type 8, to promote proliferation despite antiproliferative stimuli, including mitotic errors such as anaphase bridges, micronuclei, and chromothripsis. The mechanisms \u03b2-HPV uses to overcome these challenges are not yet fully elucidated. This paper addresses one possible mechanism by proposing that \u03b2-HPVs suppress cGAS-STING signaling to promote proliferation under conditions that would typically initiate an innate immune response, resulting in apoptosis or senescence. We found that \u03b2-HPVs can impair cGAS-STING signaling at a post-translational modification level and play a role in broadly downregulating innate immune-associated genes. Similarly, alpha human papillomaviruses (\u03b1-HPVs) display the ability to downregulate many of the same interferon-inducible genes. This suggests that there is a shared need between \u03b2-HPV and \u03b1-HPVs to target innate immune responses.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00859-25","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:00:11Z","timestamp":1772114411000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Cutaneous human papillomavirus E6 impairs the cGAS-STING pathway"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4027-8143","authenticated-orcid":false,"given":"Grant","family":"Brooke","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05p1j8758","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Biology, Kansas State University","place":["Manhattan, 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