TY - JOUR
T1 - The Tetraspanin CD81 Is a Host Factor for Chikungunya Virus Replication
AU - Lasswitz, Lisa
AU - Zapatero-Belinchón, Francisco J.
AU - Moeller, Rebecca
AU - Hülskötter, Kirsten
AU - Laurent, Timothée
AU - Carlson, Lars Anders
AU - Goffinet, Christine
AU - Simmons, Graham
AU - Baumgärtner, Wolfgang
AU - Gerold, Gisa
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - alphavirus
KW - arenavirus
KW - CD81
KW - CHIKV
KW - coronavirus
KW - KEYWORDS chikungunya virus
KW - replication
KW - tetraspanin
U2 - 10.1128/mbio.00731-22
DO - 10.1128/mbio.00731-22
M3 - Article
SN - 2161-2129
VL - 13
JO - mBio
JF - mBio
IS - 3
ER -