Animal pneumoviruses: molecular genetics and pathogenesis

Abstract

Pneumoviruses are single-stranded, negative-sense, nonsegmented RNA viruses of the family Paramyxoviridae, subfamily Pneumovirinae, and include pathogens that infect humans (respiratory syncytial virus and human metapneumovirus), domestic mammals (bovine, ovine, and caprine respiratory syncytial viruses), rodents (pneumonia virus of mice), and birds (avian metapneumovirus). Among the topics considered in this review are recent studies focused on the roles of the individual virus-encoded components in promoting virus replication as well as in altering and evading innate antiviral host defenses. Advances in the molecular technology of pneumoviruses and the emergence of recombinant pneumoviruses that are leading to improved virus-based vaccine formulations are also discussed. Since pneumovirus infection in natural hosts is associated with a profound inflammatory response that persists despite adequate antiviral therapy, we also review the recent experimental treatment strategies that have focused on combined antiviral, anti-inflammatory, and immunomodulatory approaches.

FIG. 1.

Schematic of the pneumovirus particle. The RNA genome associates with viral proteins to form the helical nucleocapsid structure (represented on the right and in the center of the virion on the left). The proteins consist of the nucleocapsid protein (N), the phosphoprotein (P), and the large polymerase (L) protein. The M2-1 protein is also thought to be present in this complex (not shown). The nucleocapsid structure is surrounded by the matrix (M) protein, which forms a link between the nucleocapsid and the lipid membrane of the virus particle. Embedded in the lipid membrane are the attachment (G) glycoprotein, the fusion (F) protein, and the small hydrophobic (SH) protein (not shown).

FIG. 2.

Genomic structures of viruses of the family Paramyxoviridae. The subfamilies, genera, and representative viruses are as indicated. *, pneumonia virus of mice is similar, without the M2-L gene overlap.

FIG. 3.

Diagrammatic representation of the organization of the pneumovirus M2-1 and M2-2 genes. The grey bar represents the M2-1 open reading frame, and the white bar represents the M2-2 open reading frame. The positions of the translation initiation and termination codons of are identified. aa, amino acids.