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- Title
Host-Dependent Modifications of Packaged Alphavirus Genomic RNA Influence Virus Replication in Mammalian Cells.
- Authors
Crawford, John M.; Yan, Liewei L.; Zaher, Hani; Hardy, Richard W.
- Abstract
Alphaviruses must interact efficiently with two distinct host environments in order to replicate and transmit between vertebrate and mosquito hosts. Some host-origin-dependent differences in virus particle composition that appear to facilitate the transmission cycle are known. However, the impact of host-mediated modification of packaged viral genomic RNA on subsequent infection has not been previously investigated. Here we show that in human (HEK-293) cells, mosquito-derived Sindbis virus (SINV) replicates and spreads faster, producing a more infectious virus than its mammalian-derived counterpart. This enhanced replication is neither a result of differences in the stability nor the production of the infecting genomic RNA. Nevertheless, purified genomic RNA from mosquito-derived SINV established infection in HEK-293 cells more efficiently than that of mammalian-derived SINV, indicating that the genomic RNA itself is different between the two producing hosts and this difference is a determinant of infection. In agreement with this idea, we show that mosquito-derived SINV genomic RNA is a more active template for translation than mammalian-derived SINV genomic RNA, and we attribute this difference to host-dependent changes in modification of packaged genomic RNA as determined by LC/MS-MS. Our data support the hypothesis that among other factors, the host-dependent modification profile of the packaged vRNA is likely to play an important role in the efficiency of SINV infection and replication in mammalian cells.
- Subjects
ALPHAVIRUSES; VIRAL replication; RNA viruses; RNA; RNA modification &; restriction
- Publication
Viruses (1999-4915), 2022, Vol 14, Issue 12, p2606
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v14122606