{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:14:37Z","timestamp":1785420877804,"version":"3.56.0"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"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":[[2026,5,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>The hepatitis C virus (HCV) p7 protein is a viroporin essential for the production of infectious virus particles and has been implicated in regulating Core protein localization. Here, we identify a previously unrecognized role of p7 in modulating Core maturation through interaction with host signal peptide peptidase (SPP), a mechanism that remains intact even in ion-channel deficient mutants. Using a transient expression system, we show that p7 from genotype 1a (H77S) delays SPP-mediated cleavage of full-length Core (fl-Core) to mature Core (m-Core), while genotype 2a (JFH1) p7 exerts a weaker inhibitory effect. Both p7 variants bind endogenous SPP, but JFH1 p7 shows reduced affinity, correlating with diminished inhibition of Core processing. A conserved leucine-rich motif (L51\u201355) in the p7 C-terminus is essential for SPP binding; its mutation disrupts Core processing and markedly reduces infectious virus production. Moreover, fl-Core preferentially associates with E1 glycoprotein compared to m-Core, supporting its role in virion assembly. These findings uncover a mechanism by which p7 regulates the timing of Core maturation via SPP interaction to promote efficient HCV particle assembly.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Hepatitis C virus (HCV) assembly depends on the tightly regulated coordination of viral structural proteins and host factors. While p7 is well-known for its viroporin activity, its role in viral protein maturation has remained unclear. This study uncovers a novel function of p7 in modulating Core protein processing via interaction with host signal peptide peptidase (SPP). We identify a conserved leucine-rich motif in p7 essential for this interaction and demonstrate that delayed Core maturation enhances Core-E1 association and promotes efficient virus assembly. These findings expand our understanding of HCV morphogenesis and highlight the p7-SPP axis as a potential target for antiviral intervention.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00288-26","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:00:17Z","timestamp":1776430817000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Hepatitis C virus p7 regulates Core protein processing via signal peptide peptidase to promote virion assembly"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2778-977X","authenticated-orcid":true,"given":"Ming-Jhan","family":"Wu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Texas Medical Branch at 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