{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:45:47Z","timestamp":1793144747672,"version":"4.5.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82325034"],"award-info":[{"award-number":["82325034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,11,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Macrophages and dendritic cells (DCs) are important targets for HIV-1 replication\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Myeloid cells are collectively more resistant to HIV-1 infection than CD4\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes, but interleukin (IL)-4 has been observed to promote macrophage susceptibility to HIV-1 infection. However, the mechanism remains unclear. Herein, we found that IL-4 enhanced HIV-1 infection in myeloid lineage macrophages by downregulating the novel antiviral factor gap junction protein beta 2 (GJB2) located on the cell membrane. In the absence of GJB2, the IL-4-mediated enhancement of HIV-1 replication was largely impaired in primary macrophages. Conversely, IL-6-mediated enhancement of HIV-1 infection was unaffected by GJB2 depletion. GJB2 was constitutively expressed in myeloid cells but not in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and GJB2 silencing enhanced HIV-1 transmission in macrophages and DCs. Additionally, GJB2 required Ca2\n                      <jats:sup>+<\/jats:sup>\n                      to exert its antiviral activity by interfering with HIV-1 attachment to target cells. Because IL-4 downregulated GJB2 expression to enhance HIV-1 infection in macrophages, GJB2 may be a novel target for the treatment of HIV-1 infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      HIV-1 primarily targets two groups of cells\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      : CD4\n                      <jats:sup>+<\/jats:sup>\n                      T lymphocytes and myeloid lineage cells, such as macrophages and dendritic cells. Although myeloid cells are more resistant to HIV-1 infection than CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, some cytokines, including interleukin (IL)-4 and IL-6, promote myeloid cell infection. Gap junction protein beta 2 (GJB2) is particularly relevant in the field of auditory science. Here, we identified GJB2 as a novel antiviral factor by demonstrating that IL-4-mediated reduction in GJB2 levels enhanced HIV-1 infection in myeloid cells. Interestingly, GJB2 expression was regulated by IL-4 but not by interferons. The reduction in GJB2 levels was inversely correlated with increased HIV-1 infection levels, suggesting the potential of GJB2 for combating HIV\/AIDS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01626-25","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:00:32Z","timestamp":1758542432000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["IL-4 downregulates gap junction protein connexin 26 to promote HIV-1 infection in macrophages"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6082-135X","authenticated-orcid":false,"given":"Shumei","family":"Wang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04wjghj95","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Health Commission Key Laboratory 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