title: Noncapped Alphavirus Genomic RNAs and Their Role during Infection.
abstract: Alphaviruses are enveloped positive-sense RNA viruses that exhibit a wide host range consisting of vertebrate and invertebrate species. Previously we have reported that the infectivity of Sindbis virus (SINV), the model alphavirus, was largely a function of the cell line producing the viral particles. Mammalian-cell-derived SINV particles, on average, exhibit a higher particle-to-PFU ratio than mosquito cell-derived SINV particles. Nevertheless, the outcome of nonproductive infection, the molecular traits that determine particle infectivity and the biological importance of noninfectious particles were, prior to this study, unknown. Here, we report that the incoming genomic RNAs of noninfectious SINV particles undergo rapid degradation following infection. Moreover, these studies have led to the identification of the absence of the 5' cap structure as a primary molecular determinant of particle infectivity. We show that the genomic RNAs of alphaviruses are not universally 5' capped, with a significant number of noncapped genomic RNA produced early in infection. The production of noncapped viral genomic RNAs is important to the establishment and maintenance of alphaviral infection.
  
  
  OBJECTIVE
  This report is of importance to the field of virology for three reasons. First, these studies demonstrate that noncapped Sindbis virus particles are produced as a result of viral RNA synthesis. Second, this report is, to our knowledge, the first instance of the direct measurement of the half-life of an incoming genomic RNA from a positive-sense RNA virus. Third, these studies indicate that alphaviral infection is likely a concerted effort of infectious and noninfectious viral particles.
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Sokoloski
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Haist
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Morrison
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana, USA sumukhop@indiana.edu rwhardy@indiana.edu.
authors.forename: S
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana, USA sumukhop@indiana.edu rwhardy@indiana.edu.
authors.forename: R W
authors.initials: RW
authors.lastname: Hardy
mesh_terms: D018354:Alphavirus Infections / Q000821:virology*; D000818:Animals; D002460:Cell Line; D016679:Genome, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D012315:RNA Caps / Q000378:metabolism*; D020871:RNA Stability; D012367:RNA, Viral / Q000378:metabolism*; D012845:Sindbis Virus / Q000502:physiology*
chemical_list: D012315:RNA Caps; D012367:RNA, Viral
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