{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:07:13Z","timestamp":1791356833525,"version":"4.3.1"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"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":[[2025,7,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>We have previously found that human apolipoprotein E (apoE) is enriched on the envelope of infectious hepatitis B virus (HBV) and plays an important role in HBV infection and morphogenesis. Recently, we have demonstrated that the low-density lipoprotein receptor (LDLR) is required for efficient HBV infection. LDLR is a known apoE-binding receptor. Additionally, heparan sulfate proteoglycans (HSPGs) serve as apoE-binding receptors. HSPGs are implicated in HBV infection as HBV cell attachment receptors. HSPGs are composed of heparan sulfate glycosaminoglycans covalently attached to core proteins, including syndecans (SDC1\u2013SDC4) and glypicans (GPC1\u2013GPC6). GPC5 was previously reported as an HBV entry-promoting factor. In the present study, we have identified SDC2 as another cell attachment receptor promoting HBV infection. Small interfering RNA (siRNA)-induced silencing of SDC2 expression resulted in a significant reduction of HBV infection. Likewise, SDC2 gene knockout decreased the susceptibility of hepatocytes to HBV infection. However, the defective HBV infection in the SDC2-deficient hepatocytes could be fully restored by ectopic SDC2 expression. The importance of SDC2 in HBV infection was validated using primary human hepatocytes. Moreover, SDC2 deficiency lowered preS1- and apoE-binding and consequently HBV attachment to the surface of hepatocytes. Collectively, our findings suggest that SDC2 functions as an HBV cell attachment receptor.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Many different DNA and RNA viruses use HSPGs as cell attachment receptors. HSPGs are composed of core proteins and covalently attached heparan sulfate glycosaminoglycans. Individual SDCs and GPCs play distinct roles in the mediation of cell attachment of different viruses. GPC5 was previously found to promote HBV infection. However, the role of SDCs in HBV infection has not been experimentally examined. In the present study, we have identified SDC2 as an HBV cell attachment receptor. We further found that SDC2-deficient hepatocytes are much less susceptible to preS1- and apoE-binding. These findings suggest that SDC2 promote HBV infection likely through interactions with apoE and preS1, both of which are present on the surface of HBV envelope and contain HSPG-binding sites.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00796-25","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T09:00:08Z","timestamp":1750928408000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Syndecan 2 proteoglycan serves as a hepatitis B virus cell attachment receptor"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2620-4947","authenticated-orcid":true,"given":"Sachin Kumar","family":"Tripathi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0207ad724","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Wake Forest University 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