Paramyxoviruses and RhabdovirusesParamyxoviridae and Rhabdoviridae

VirionVirion

GenomeGenome

Genes and proteinsGenes and proteins

Viruses and hostsViruses and hosts

DiseasesDiseases

Distinctive characteristicsDistinctive characteristics

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 RhabdovirusesParamyxoviridae and Rhabdoviridae

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

Paramyxoviruses and RhabdovirusesParamyxoviridae 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 RhabdovirusesParamyxoviridae 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 RhabdovirusesParamyxoviridae 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 RhabdovirusesParamyxoviridae 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).

Paramyxoviruses and RhabdovirusesParamyxoviridae and Rhabdoviridae

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

Fig. 20.7 Alternative models for transcription of mononegavirus genome RNA.

(a) Multiple-promoter model: RNA polymerases (gray spheres) initiate transcriptionindependently at promoters just upstream of each viral gene.

(b) Single entry model: RNA polymerases initiate transcription only at the 3 end of the genome,

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

B lymphocytes Coiled-coil Dendritic cells Encephalitis Fusion peptide Gangliosides Hemagglutination Hemagglutinin Interferon Nested set Neuraminidase

Pseudotyping Sialic acid Subacute sclerosing

panencephalitis (SSPE) Synctia (singular: syncytium) T lymphocytes Type I integral membrane

protein Type II integral membrane

protein