defective interfering viral particles in acute dengue infections有缺陷的影响在急性登革热感染病毒颗粒.pdfVIP

Defective Interfering Viral Particles in Acute Dengue Infections 1 1 1 1 2 1 Dongsheng Li , William B. Lott , Kym Lowry , Anita Jones , Hlaing Myat Thu , John Aaskov * 1 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia, 2 Virology Research Division, Department of Medical Research, Yangon, Myanmar 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 39 and 59 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. DE