Development and applications of single-cycle infectious influenza A virus (sciIAV)

Abstract

The diverse host range, high transmissibility, and rapid evolution of influenza A viruses justify the importance of containing pathogenic viruses studied in the laboratory. Other than physically or mechanically changing influenza A virus containment procedures, modifying the virus to only replicate for a single round of infection similarly ensures safety and consequently decreases the level of biosafety containment required to study highly pathogenic members in the virus family. This biological containment is more ideal because it is less apt to computer, machine, or human error. With many necessary proteins that can be deleted, generation of single-cycle infectious influenza A viruses (sciIAV) can be achieved using a variety of approaches. Here, we review the recent burst in sciIAV generation and summarize the applications and findings on this important human pathogen using biocontained viral mimics.

Replication-competent fluorescent-expressing influenza B virus

“…With the development of reverse genetics techniques, similar approaches have been implemented for the generation and characterization of replication-competent fluorescentexpressing IAVs (Avilov et al, 2012;Baker et al, 2015b;Fiege and Langlois, 2015;Fukuyama et al, 2015;Manicassamy et al, 2010;Nogales et al, 2015Nogales et al, , 2014aReuther et al, 2015;Rimmelzwaan et al, 2011). However, similar methods have not been used for the generation of recombinant fluorescent-expressing IBVs.…”

Current status and evolving approaches to African swine fever vaccine development

“…On the other hand, single‐cycle viruses are defective in certain viral gene circuits essential for virus assembly (Lauring et al, ; Jorge & Dellagostin, 2017). The essential concept behind single‐cycle viruses is that the biological art of genetic modification is different from gene‐deleted live virus attenuation/replication‐defective viruses in that the virus replicates in situ , but the assembly of virus particle is disabled (Crosby & Barry, ; Jorge & Dellagostin, ; Nogales, Baker, Domm, & Martínez‐Sobrido, ).…”

“…Besides, stable cell lines complementing the deleted proteins essential for virus assembly should be generated. Therefore, the construction of single‐cycle ASFV would be a safe vaccine as developed for other viruses (Murakami, Terasaki, Ramirez, Morrill, & Makino, ; Nogales et al, ). Like LAVs, single‐cycle ASF vaccines could mimic the acute nature of ASFV infection and activate the cellular immune response.…”

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

“…A significant deterrent to automated anti-RABV drug discovery, for instance, is the BSL2/3 containment requirements imposed by replication-competent RABVs and mandatory rabies vaccination as well restriction to the laboratory of not vaccinated people.. Based on the original reverse genetics system developed for the SAD-B19 RABV strain [64], however, minireplicon systems and single-cycle reporter RABV viruses were developed that allow study of the RABV polymerase activity and in-cell replication in a BSL2 setting [65][66][67][68][69][70][71][72][73]. Analogous to the precedent set by successful screens employing single-cycle HIV, hepatitis C virus, and influenza virus reporter strains [74][75][76], the single-cycle based approach in particular offers an exciting drug discovery perspective. Transient-transfection based minigenome drug screens have furthermore been attempted to identify, for instance, Ebola virus polymerase inhibitors [77][78][79].…”