Parainfluenza Viruses

Abstract Parainfluenza viruses are enveloped viruses that contain nonsegmented negative‐strand genomic ribonucleic acid (RNA). Replication of these viruses begins with entry by attachment and fusion, followed by genomic transcription and replication. Next, the de novo synthesised viral components are trafficked to assembly sites at the plasma membrane where newly formed virions bud out from the cell. These viruses are respiratory pathogens which act as the causative agents for croup, bronchiolitis and pneumonia. As a group, the parainfluenza viruses are second only to human respiratory syncytial virus as the cause of acute paediatric respiratory tract disease and are responsible for hundreds of thousands of additional U.S. hospitalisations per year. Despite their clinical importance, licensed vaccines or antiviral compounds for prevention or treatment of parainfluenza viruses are not currently available, making understanding the pathogenesis of these viruses critical for antiviral drug and vaccine development. Key Concepts: Parainfluenza viruses are enveloped, nonsegmented negative‐strand RNA viruses, which cause respiratory infections. The structure of the virion consists of glycoprotein spikes protruding from a lipid envelope under which lies the matrix protein surrounding the viral nucleocapsid, consisting of viral RNA encapsidated by nucleoprotein and associated with the polymerase complex. Specific interactions between the two envelope glycoproteins HN and F are necessary for efficient virus infection. Because the viral genome is negative‐stranded RNA, an intermediate step is required for production of progeny viral genomes. Newly synthesised viral nucleocapsids are transported to the assembly site at the plasma membrane utilising the microtubule network. Pathogenicity of parainfluenza viruses is highly dependent on the anti‐interferon activity of the viral accessory proteins. Infectious virus can be created from a complementary deoxyribonucleic acid (cDNA) clone of the viral RNA genome, which is termed reverse genetics. The development of vaccines against parainfluenza viruses currently include intranasally administered vaccines attenuated by cold‐passage, host range attenuation, chimeric vaccine constructs, or the introduction of attenuating mutations through the use of reverse genetics.