Paramyxoviruses and Rhabdoviruses Paramyxoviridae and Rhabdoviridae Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics

Paramyxoviruses and Rhabdoviruses Paramyxoviridae and Rhabdoviridae Virion Paramyxoviruses: spherical, diameter 150–300 nm, also found as filaments. Rhabdoviruses: bullet-shaped rods, 180 75 nm. Envelope derived from plasma membrane. Coiled helical nucleocapsid.

Paramyxoviruses and Rhabdoviruses Paramyxoviridae and Rhabdoviridae Genome Linear ssRNA, negative sense. Single segment. Paramyxoviruses: 15–18 Kb. Rhabdoviruses: 11–12 Kb.

Paramyxoviruses and Rhabdoviruses Paramyxoviridae and Rhabdoviridae Genes and proteins Five to nine genes, transcribed in series from 3 end of genome by viral RNA polymerase. Most genes produce a single mRNA and a single protein. Most proteins packaged in virion: Nucleocapsid protein (N) RNA polymerase cofactor and accessory proteins (P/C/V) Matrix protein (M) Fusion protein (F) Hemagglutinin/neuraminidase,

Paramyxoviruses and Rhabdoviruses Paramyxoviridae and Rhabdoviridae Viruses and hosts Paramyxoviruses: Humans: measles, mumps, respiratory syncytial, parainfluenza viruses Animals: viruses infecting birds, pigs, dogs, cats, seals, whales, etc., Sendai (mice), Newcastle disease (chickens), canine distemper, rinderpest (cattle) viruses Rhabdoviruses: Humans: rabies virus Cattle: vesicular stomatitis virus Numerous rhabdoviruses infecting bats, fish, insects, plants

Paramyxoviruses and Rhabdoviruses Paramyxoviridae and Rhabdoviridae Diseases Paramyxoviruses: several important childhood diseases, including measles, mumps, respiratory diseases in humans; canine distemper, rinderpest. Emerging paramyxoviruses Hendra and Nipah cause respiratory and neurological disease in pigs, humans, horses, and bats. Rhabdoviruses: rabies (fatal encephalitis in humans), transmitted by bites of infected animals; vesicular stomatitis virus in cattle. Numerous insect and plant diseases.

Paramyxoviruses and Rhabdoviruses Paramyxoviridae and Rhabdoviridae Distinctive characteristics RNA-dependent RNA polymerase in virion transcribes genome into mRNAs. Single transcriptional promoter at 3 end of RNA; mRNAs made by a start-stop mechanism. Full-length genome or antigenome RNA is always present as assembled nucleocapsids. Some paramyxoviruses “edit” P mRNA at a specific site, generating mRNAs with distinct protein-coding capacities. Some paramyxoviruses induce cell-cell fusion, producing multinucleated cells (syncytia).

Virion The mononegaviruses: a group of related negative-strand RNA viruses Single RNA genome packaged in a helical nucleocapsid Envelope derived from host plasma membrane Viral RNA polymerase packaged in the virion mRNAs made by a start-stop mechanism

Virion Rabies is a fatal human encephalitis caused by a rhabdovirus Infect wide variety of hosts Rabies virus is of significant concern to human health Infected by virus-containing saliva from bites of infected animals Infection results in a fatal encephalitis Measles is a serious childhood disease caused by a paramyxovirus

Virion Paramyxovirus and rhabdovirus virions have distinct morphologies Structure of paramyxoviruses

Virion Paramyxovirus and rhabdovirus virions have distinct morphologies Structure of rhabdoviruses

Virion Viral envelope proteins are responsible for receptor binding and fusion with cellular membranes Fig. 20.3 Schematic diagram of paramyxovirus virion.

Genome Fig. 20.4 Envelope proteins of paramyxoviruses.

Genome Genome RNA is contained within helical nucleocapsids Structure of paramyxovirus helical nucleocapsid

Genome Paramyxoviruses enter the cell by fusion with the plasma membrane at neutral pH Binding Sendai : HN - sialic acid Measles : H - CD46, CD150/SLAM Upon binding, F protein undergoes conformational change that allows insertion of fusion peptide to plasma membrane.

Genome Gene order is conserved among different paramyxoviruses and rhabdoviruses Leader region Signals for initiation of RNA synthesis Signals for packaging of full-length RNA genome No cap, no poly A tail Intergenic sequence Controls txn termination, polyadenylation, reinitiation Fig. 20.6 Paramyxovirus genome RNA.

Genes and Proteins Viral messenger RNAs are synthesized by an RNA polymerase packaged in the virion Viral RNA polymerase initiates transcription exclusively at the 3’ end of the viral genome

Genes and Proteins (a) Multiple-promoter model: RNA polymerases (gray spheres) initiate transcription independently at promoters just upstream of each viral gene. (b) Single entry model: RNA polymerases initiate transcription only at the 3 end of the genome, Fig. 20.7 Alternative models for transcription of mononegavirus genome RNA.

Genes and Proteins The promoter for plus-strand RNA synthesis consists of two sequence elements separated by one turn of the ribonucleoprotein helix mRNAs are synthesized sequentially from the 3 to the 5 end of the genome RNA

Genes and Proteins Fig. 20.8 Paramyxovirus transcription and replication.

Genes and proteins The P/C/V gene codes for several proteins by using alternative translational starts and by mRNA “editing” Fig. 20.9 Sendai virus P/C/V gene: open reading frames, translational start sites, and “stuttering” site.

Genes and proteins Functions of P, C, and V proteins P : cofactor required for viral RNA synthesis directs binding of L to the promoter V : not normally required for replication interferes with host mechanisms that reduce viral replication C : required for formation of infectious virion exact roles not understood

Genes and proteins N protein levels control the switch from transcription to genome replication Virions are assembled at the plasma membrane Envelope protein inserted into plasma membrane Matrix protein associates with cytoplasmic face of p.m. Nucleocapsid interact w/ matrix protein Virions are made by budding from p.m.

Key Terms Pseudotyping B lymphocytes Sialic acid Coiled-coil Subacute sclerosing panencephalitis (SSPE) Synctia (singular: syncytium) T lymphocytes Type I integral membrane protein Type II integral membrane protein B lymphocytes Coiled-coil Dendritic cells Encephalitis Fusion peptide Gangliosides Hemagglutination Hemagglutinin Interferon Nested set Neuraminidase