Defective interfering viral particles in acute dengue infections.

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
PLoS ONE (Impact Factor: 3.53). 01/2011; 6(4):e19447. DOI: 10.1371/journal.pone.0019447
Source: PubMed

ABSTRACT While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3' and 5' ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6-36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Flaviviruses are a genus of (+)ssRNA (positive ssRNA) enveloped viruses that replicate in the cytoplasm of cells of diverse species from arthropods to mammals. Many are important human pathogens such as DENV-1-4 (dengue virus types 1-4), WNV (West Nile virus), YFV (yellow fever virus), JEV (Japanese encephalitis virus) and TBEV (tick-borne encephalitis). Given their RNA genomes it is not surprising that flaviviral life cycles revolve around critical RNA transactions. It is these we highlight in the present article. First, we summarize the mechanisms governing flaviviral replication and the central role of conserved RNA elements and viral protein-RNA interactions in RNA synthesis, translation and packaging. Secondly, we focus on how host RNA-binding proteins both benefit and inhibit flaviviral replication at different stages of their life cycle in mammalian hosts. Thirdly, we cover recent studies on viral non-coding RNAs produced in flavivirus-infected cells and how these RNAs affect various aspects of cellular RNA metabolism. Together, the article puts into perspective the central role of flaviviral RNAs in modulating both viral and cellular functions.
    The Biochemical journal. 09/2014; 462(2):215-230.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Erwin Schrödinger‘s question “What is life?” received the answer for decades of “physics + chemistry”. The concepts of Alain Turing and John von Neumann introduced a third term: “information”. This led to the understanding of nucleic acid sequences as a natural code. Manfred Eigen adapted the concept of Hammings “sequence space”. Similar to Hilbert space, in which every ontological entity could be defined by an unequivocal point in a mathematical axiomatic system, in the abstract ”sequence space” concept each point represents a unique syntactic structure and the value of their separation represents their dissimilarity. In this concept molecular features of the genetic code evolve by means of self-organisation of matter. Biological selection determines the fittest types among varieties of replication errors of quasi-species. The quasi-species concept dominated evolution theory for many decades. In contrast to this, recent empirical data on the evolution of DNA and its forerunners, the RNA-world and viruses indicate cooperative agent-based interactions. Group behaviour of quasi-species consortia constitute de novo and arrange available genetic content for adaptational purposes within real-life contexts that determine epigenetic markings. This review focuses on some fundamental changes in biology, discarding its traditional status as a subdiscipline of physics and chemistry.
    World Journal of Biological Chemistry. 08/2014; 5(3):279-285.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetically diverse RNA viruses like dengue viruses (DENVs) segregate into multiple, genetically distinct, lineages that temporally arise and disappear on a regular basis. Lineage turnover may occur through multiple processes such as, stochastic or due to variations in fitness. To determine the variation of fitness, we measured the distribution of fitness within DENV populations and correlated it with lineage extinction and replacement. The fitness of most members within a population proved lower than the aggregate fitness of populations from which they were drawn, but lineage replacement events were not associated with changes in the distribution of fitness. These data provide insights into variations in fitness of DENV populations, extending our understanding of the complexity between members of individual populations.
    PLoS ONE 09/2014; 9(9):e107264. · 3.53 Impact Factor

Full-text (3 Sources)

Available from
Jun 1, 2014