subtype specific differences in ns5a domain ii reveals involvement of proline at position 310 in cyclosporine susceptibility of hepatitis c virus亚型的具体差异ns5a域ii揭示脯氨酸在310位置参与环孢霉素c型肝炎病毒的易感性.pdfVIP

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subtype specific differences in ns5a domain ii reveals involvement of proline at position 310 in cyclosporine susceptibility of hepatitis c virus亚型的具体差异ns5a域ii揭示脯氨酸在310位置参与环孢霉素c型肝炎病毒的易感性.pdf

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subtype specific differences in ns5a domain ii reveals involvement of proline at position 310 in cyclosporine susceptibility of hepatitis c virus亚型的具体差异ns5a域ii揭示脯氨酸在310位置参与环孢霉素c型肝炎病毒的易感性

Viruses 2012, 4, 3303-3315; doi:10.3390/v4 123303 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Article Subtype Specific Differences in NS5A Domain II Reveals Involvement of Proline at Position 310 in Cyclosporine Susceptibility of Hepatitis C Virus Israr-ul H. Ansari 1 and Rob Striker 1,2,* 1 Department of Medicine, University of Wisconsin-Madison, WI 53706, USA; E-Mail: ihansari@ 2 W. S. Middleton Memorial Veteran’s Hospital, Madison, WI 53706, USA * Author to whom correspondence should be addressed; E-Mail: rtstriker@; Tel.: +1-608-263-5794; Fax: +1-608-262-8418. Received: 11 October 2012; in revised form: 17 November 2012 / Accepted: 20 November 2012 / Published: 22 November 2012 Abstract: Hepatitis C virus (HCV) is susceptible to cyclosporine (CsA) and other cyclophilin (CypA) inhibitors, but the genetic basis of susceptibility is controversial. Whether genetic variation in NS5A alters cell culture susceptibility of HCV to CypA inhibition is unclear. We constructed replicons containing NS5A chimeras from genotypes 1a, 2a and 4a to test how variation in carboxy terminal regions of NS5A altered the genotype 1b CsA susceptibility. All chimeric replicons including genotype 1b Con1LN-wt replicon exhibited some cell culture sensitivity to CsA with genotype 4a being most sensitive and 1a the least. The CypA binding pattern of truncated NS5A genotypes correlated wi