The C-terminal helical domain of dengue virus precursor membrane protein is involved in virus assembly and entry.

Hsieh SC, Zou G, Tsai WY, Qing M, Chang GJ, Shi PY, Wang WK.

Citation

Hsieh SC, Zou G, Tsai WY, Qing M, Chang GJ, Shi PY, Wang WK. (2011) The C-terminal helical domain of dengue virus precursor membrane protein is involved in virus assembly and entry. Virology 410(1):170-180.

Abstract

The role of the alpha-helical domain (MH) of dengue virus (DENV) precursor membrane protein in replication was investigated by site-directed mutagenesis. Proline substitutions of three residues (120, 123 and 127) at the C-terminus, but not those at the N-terminus of MH domain, reduced the virus-like particles of DENV1, DENV2 and DENV4 detected in supernatants. In a DENV2 replicon trans-packaging system, these three mutations suppressed particles detected; two of them (I123P and V127P) also affected viral entry. In the context of DENV2 genome-length RNA, all three mutations reduced virion assembly and virus spreading in cell culture. Analysis of revertants showed that mutation A120P could partially support viral infection cycle; in contrast, mutations I123P and V127P were lethal, and adaptations of I123P?I123L and V127P?V127L were required to restore the viral infection cycle. These findings demonstrate that the C-terminus of the MH domain is involved in both assembly and entry of DENV.