Boi Stefano, Rosenke Kyle, Hansen Ethan, Hendrick Duncan, Malik Frank, Evans Leonard H
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
Virology. 2016 Dec;499:136-143. doi: 10.1016/j.virol.2016.07.009. Epub 2016 Sep 19.
We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses.
我们已在小鼠模型中证明,感染逆转录病毒不仅会导致外源性和内源性γ逆转录病毒之间产生重组体,还会通过将整个多嗜性前病毒转录本伪型化并促进其感染性传播到新细胞,从而导致内源性前病毒的动员。然而,这种情况发生的频率、动力学以及被动员的内源性前病毒的身份尚不清楚。在这里,我们发现这些被动员的转录本在感染仅一天后就能被检测到。它们在感染早期比重组多嗜性病毒占优势,在疾病过程中持续存在,并且由多种不同的多嗜性前病毒组成。未检测到其他内源性逆转录病毒元件,如胞内A颗粒(IAPs)。内源性转录本整合到新细胞中可能导致转录控制丧失和表达升高,这可能通过促进多嗜性重组病毒的产生而有助于发病机制。