Viral subversion of apoptotic enzymes: escape from death row.
To prolong cell viability and facilitate replication, viruses have evolved multiple mechanisms to inhibit the host apoptotic response. Cellular proteases such as caspases and serine proteases are instrumental in promoting apoptosis. Thus, these enzymes are logical targets for virus-mediated modulation to suppress cell death. Four major classes of viral inhibitors antagonize caspase function: serpins, p35 family members, inhibitor of apoptosis proteins, and viral FLICE-inhibitory proteins. Viruses also subvert activity of the serine proteases, granzyme B and HtrA2/Omi, to avoid cell death. The combined efforts of viruses to suppress apoptosis suggest that this response should be avoided at all costs. However, some viruses utilize caspases during replication to aid virus protein maturation, progeny release, or both. Hence, a multifaceted relationship exists between viruses and the apoptotic response they induce. Examination of these interactions contributes to our understanding of both virus pathogenesis and the regulation of apoptotic enzymes in normal cellular functions.
Best
Sonja M
SM
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. sbest@niaid.nih.gov
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D012697:Serine Endopeptidases / Q000378:metabolism; D015843:Serpins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism; D014779:Virus Replication; D014780:Viruses / Q000472:pathogenicity*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D015843:Serpins; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; D012697:Serine Endopeptidases; D020169:Caspases