Detalle de: Poxvirus-encoded TNF receptor homolog dampens inflammation and protects from uncontrolled lung pathology during respiratory infection

Significance Viruses have coevolved with their hosts and developed strategies to dampen, evade, or subvert the host immune response to provide an advantage to the virus. We show that ectromelia virus (ECTV) encodes a TNF receptor (TNFR) homolog, which provides an advantage to the host and virus by dampening TNF levels and inflammation. Infection of ECTV-resistant mice with a mutant virus lacking viral TNFR (vTNFR) caused significant lung pathology and death due to secretion of excessive levels of TNF and other inflammatory cytokines. In vitro, recombinant vTNFR from ECTV and other orthopoxviruses bound to membrane-associated TNF and down-regulated inflammatory gene expression through reverse signaling. vTNFR benefits the host by enabling survival, potentially facilitating virus spread, which should advantage the virus.