Abortive Infection of Animal Cells: What Goes Wrong

Abstract

Even if a virus successfully binds to a cell, defects in any of the downstream steps of the viral life cycle can preclude the production of infectious virus particles. Such abortive infections are likely common in nature and can provide fundamental insights into the cell and host tropism of viral pathogens. Research over the past 60 years has revealed an incredible diversity of abortive infections by DNA and RNA viruses in various animal cell types. Here we discuss the general causes of abortive infections and provide specific examples from the literature to illustrate the range of abortive infections that have been reported. We also discuss how abortive infections can have critical roles in shaping host immune responses and in the development of virus-induced cancers. Finally, we describe how abortive infections can be applied to basic and clinical research, underscoring the importance of understanding these fascinating aspects of virus biology.

Keywords: abortive infection; host immune response; host range; oncogenic virus; viral immune evasion; virus-host interactions.

Figure 1.

Possible infection outcomes. Viral infection of permissive cells can result in productive infections that generate new virus particles (A) or non-productive latent infections, typified by little or no viral gene expression, but can reactivate later to become productive (B). Initiation of infection in non-permissive cells results in abortive infections that fail at one or more steps of the life cycle and do not produce virus particles (C). Cell survival or death may ensue in A-C. However, abnormal integration of oncogenic DNA virus genomes into cellular DNA during abortive infection can result in sustained oncogenic viral gene expression and cellular transformation when these cells are not eliminated by the immune response (D). Figure was created with biorender.com.

Figure 2.

Restriction of VV by human SAMD9 and its antagonism by K1 and C7. VV virion release into the cytoplasm results in expression of early genes (including K1L and C7L), uncoating, viral genome replication, post-replicative (intermediate/late) gene expression, and assembly. SAMD9 is activated by VV infection to bind and cleave phenylalanine tRNA (tRNA^Phe), resulting in a global arrest of mRNA translation that predominantly affects post-replicative viral mRNA translation. However, VV K1 and C7 counter this response by binding and inhibiting SAMD9 to ensure productive replication. SAMD9L, a paralog of SAMD9 may also function similarly and can also be targeted by K1 and C7 (not shown) (40, 48, 49). Cowpox virus CP77 and myxoma virus M062 proteins can also bind and inhibit SAMD9 (38, 44). Figure was created with biorender.com.

Figure 3.

Using abortive VSV infections in LD652 cells in virus-host interaction screens. Abortive infection of VSV strains encoding GFP (VSV-GFP) can be used to screen for immunosuppressive co-infecting viruses or immune evasion factors expressed from plasmids that rescue GFP expression. Host antiviral factors restricting VSV replication can also be identified by transecting dsRNAs (for RNAi) targeting host transcripts. Figure was created with biorender.com.