Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1866, Issue 3, Pages 382-394Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2018.09.012
Keywords
Interferon stimulated gene; Virus infection; Restriction factor
Categories
Funding
- NIH [AI130110, AI104483]
- Ohio State University Systems and Integrative Biology Training Program - NIH [GM068412]
- Ohio State University Interdisciplinary Program in Microbe-Host Interactions - NIH [AI112542]
- Ohio State University College of Medicine
- Gilliam Predoctoral Fellowship from the Howard Hughes Medical Institute
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Antiviral restriction factors are cellular proteins that inhibit the entry, replication, or spread of viruses. These proteins are critical components of the innate immune system and function to limit the severity and host range of virus infections. Here we review the current knowledge on the mechanisms of action of several restriction factors that affect multiple viruses at distinct stages of their life cycles. For example, APOBEC3G deaminates cytosines to hypermutate reverse transcribed viral DNA; IFITM3 alters membranes to inhibit virus membrane fusion; MXA/B oligomerize on viral protein complexes to inhibit virus replication; SAMHD1 decreases dNTP intracellular concentrations to prevent reverse transcription of retrovirus genomes; tetherin prevents release of budding virions from cells; Viperin catalyzes formation of a nucleoside analogue that inhibits viral RNA polymerases; and ZAP binds virus RNAs to target them for degradation. We also discuss countermeasures employed by specific viruses against these restriction factors, and mention secondary functions of several of these factors in modulating immune responses. These important examples highlight the diverse strategies cells have evolved to combat virus infections.
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