Your browser doesn't support javascript.
loading
The Tetraspanin CD81 Is a Host Factor for Chikungunya Virus Replication.
Lasswitz, Lisa; Zapatero-Belinchón, Francisco J; Moeller, Rebecca; Hülskötter, Kirsten; Laurent, Timothée; Carlson, Lars-Anders; Goffinet, Christine; Simmons, Graham; Baumgärtner, Wolfgang; Gerold, Gisa.
Afiliación
  • Lasswitz L; Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hanover, Germany.
  • Zapatero-Belinchón FJ; Institute for Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hanover, Hanover, Germany.
  • Moeller R; Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hanover, Germany.
  • Hülskötter K; Institute for Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hanover, Hanover, Germany.
  • Laurent T; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden.
  • Carlson LA; Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
  • Goffinet C; Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hanover, Germany.
  • Simmons G; Institute for Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hanover, Hanover, Germany.
  • Baumgärtner W; Department of Pathology, University of Veterinary Medicine Hanover, Hanover, Germany.
  • Gerold G; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden.
mBio ; 13(3): e0073122, 2022 06 28.
Article en En | MEDLINE | ID: mdl-35612284
Chikungunya virus (CHIKV) is an arthritogenic reemerging virus replicating in plasma membrane-derived compartments termed "spherules." Here, we identify the human transmembrane protein CD81 as host factor required for CHIKV replication. Ablation of CD81 results in decreased CHIKV permissiveness, while overexpression enhances infection. CD81 is dispensable for virus uptake but critically required for viral genome replication. Likewise, murine CD81 is crucial for CHIKV permissiveness and is expressed in target cells such as dermal fibroblasts, muscle and liver cells. Whereas related alphaviruses, including Ross River virus (RRV), Semliki Forest virus (SFV), Sindbis virus (SINV) and Venezuelan equine encephalitis virus (VEEV), also depend on CD81 for infection, RNA viruses from other families, such as coronaviruses, replicate independently of CD81. Strikingly, the replication-enhancing function of CD81 is linked to cholesterol binding. These results define a mechanism exploited by alphaviruses to hijack the membrane microdomain-modeling protein CD81 for virus replication through interaction with cholesterol. IMPORTANCE In this study, we discover the tetraspanin CD81 as a host factor for the globally emerging chikungunya virus and related alphaviruses. We show that CD81 promotes replication of viral genomes in human and mouse cells, while virus entry into cells is independent of CD81. This provides novel insights into how alphaviruses hijack host proteins to complete their life cycle. Alphaviruses replicate at distinct sites of the plasma membrane, which are enriched in cholesterol. We found that the cholesterol-binding ability of CD81 is important for its function as an alphavirus host factor. This discovery thus broadens our understanding of the alphavirus replication process and the use of host factors to reprogram cells into virus replication factories.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus / Virus Chikungunya / Fiebre Chikungunya Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: MBio Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Virus / Virus Chikungunya / Fiebre Chikungunya Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: MBio Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos