Double-stranded viral RNA persists in vitro and in vivo during prolonged infection of porcine reproductive and respiratory syndrome virus

Abstract

In order to study the mechanism of PRRSV persistence, an in vitro model of persistence was developed by serially passaging PRRSV-infected MARC-145 cells 109 times. Viral persistence was detected to be associated with increased double-stranded (dsRNA) in the infected cells. In PRRSV infected pigs, reduced ratio of plus to minus strands of viral RNA was observed in lymphoid tissues from PRRSV persistent pigs at 52 days post infection. Viral dsRNA was mostly detected in the germinal center during persistent infection compared to the localization of dsRNA in the inter-follicular zones during acute infection. RNA array analysis of antiviral cytokines in persistently infected lymph nodes showed that the presence of dsRNA did not stimulate antiviral immunity. These results suggest that PRRSV dsRNA functions as a mediator for viral persistence. The localization of PRRSV dsRNA in the germinal center of lymphoid tissues reveals a novel mechanism for PRRSV persistence.

A persistently replicating SARS-CoV-2 variant derived from an asymptomatic individual

“…This finding attests for the unprecedented ability of the novel isolate to manipulate cell machinery to circumvent cell death and demands for further studies to understand the molecular mechanisms underlying its persistent infection. Nidovirales and, among them, coronaviruses are prone to establish persistence both in vivo and in vitro [ 36 ]. It is well admitted that persistence results from adaptations of both the host cell and the virus [ 37 ] and that mutations in the viral genome concur to the persistence [ 38 ].…”

Host Transcriptional Response to Persistent Infection with a Live-Attenuated Porcine Reproductive and Respiratory Syndrome Virus Strain

“…It was reported previously that no significant DEGs were observed in lymphoid tissue of persistently infected animals [ 26 ]. In the current study, we identified a large number of DEGs in persistently infected animals ( Figure 2 b).…”

“…Viral RNA reads were detected in ILN of all five infected pigs. It was reported previously that PRRSV genome mainly exists in dsRNA forms in lymphoid tissues during persistent infection [26]. Since only mRNA (purified by using poly-T oligo-attached magnetic beads) was used for library construction and RNA sequencing, the viral RNA reads detected in this study must be derived from either viral genomic RNA or sub-genomic mRNA, not from dsRNA.…”

“…These regions contain multiple genes that play a role in recruitment and activation of T-cells (T-cell transcription factor 7-TCF7), chemotactic cytokines (CCL1, CCL2, and CCL8), and T-cell migration (CD34) [25]. Recently, a study of experimental infection in pigs with PRRSV-1 revealed that during persistent infection, viral proteins are minimally expressed and viral genomes exist predominantly in the form of double stranded RNA (dsRNA) [26]. Interestingly, no significant difference in host transcriptional response between persistently infected and non-infected pigs was observed in this study.…”

“…Interestingly, no significant difference in host transcriptional response between persistently infected and non-infected pigs was observed in this study. It is noteworthy that this study only analyzed a set of 189 selected swine immune genes from trachea bronchial lymph node (TBLN) tissue [26].…”