Inhibition of Antiviral Signaling Pathways by Paramyxovirus Proteins

The Paramyxoviridae family includes enveloped, negative-sense, single-stranded (ss) RNA viruses, that are major and ubiquitous disease-causing pathogens of humans and animals. Among them are important viruses that cause acute respiratory morbidity, particularly in infants, the elderly, and immunocompromised subjects of any age. The family is taxonomically divided into two subfamilies: the Paramyxovirinae, with five genera; and the Pneumovirinae, which includes two genera. The classification of the viruses is based on their genome organization, morphological and biological characteristics, and sequence relationship of the encoded proteins. To date, the paramyxovirus P gene-encoded proteins, the nonstructural (NS) (NS1 and NS2) proteins of pneumoviruses, and the envelope glycoproteins G and small hydrophobic (SH) protein have been shown to play a major role in antagonizing type I interferon (IFN) signaling and other host innate immune responses. A discussion of the inhibitory function for each of these proteins is presented in this chapter. A small hydrophobic (SH) protein (64 amino acids) is an integral membrane protein of respiratory syncytial virus (RSV). Human metapneumovirus (hMPV) expresses an SH protein that is nearly three times longer than the respiratory syncytial virus (RSV) SH and does not affect viral replication. During the early phase of RSV infection (12 to 24 h), the retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling (MAVS) complex is important in canonical pathway activation.