Paramyxoviruses and Rhabdovirus Part 2

• through bites that allows animals to change their behavior—induces aggressive behavior that allows viral spread
•  in wild areas

• reservoir: wild animals
• vector: wild animals and unvaccinated dogs and cats

Source: saliva bite is major; aerosols in bat caves with rabid bats is minor

asymptomatic period

Only three documented unvaccinated human survivors after clinical presentation

Milwaukee protocol: experimental course of treatment of an infection of rabies in a human being; treatment involves putting the patient into a chemical induced coma and administeringantiviral drugs--Jeanna Giese survived

Many other small simple viruses have a protein that is capable of binding to cells and getting inside of that cell

Hemagglutinin binds to the receptors, causing hemagglutination. 

Some H proteins also have neuraminidase activity

fusion protein that directs fusion of the membranes

Fusion proteins have hidden, hydrophobic fusion peptides that are revealed upon cleavage

F is a type I integral membrane protein

helps give virus structure underneath envelope and is involved in assembly

Underneath, there is negative sense RNA, which is spaced out

hemagglutinin and neuraminidase

They get into the cell but need to get out and neuraminidase cleaves off the receptors of infected cells to try to get away

They are type II integral membrane proteins

the receptor isn't present; it occurs after cleavage of the protein into two subunits

the viral N protein forms the helical nucleocapsid along with genome RNA 

L and P are also packaged

by fusion with the membrane at neutral pH

Sendai and closely related viruses bind to terminal sialic acid residues on gangliosides

Measles binds to CD46 (on most cells), CD150/SLAM (on B and T lymphocytes, dendriic cells, adn some monocytes, which regulate interferon production

Gene order= highly conserved

5-10 genes coding for a specific mRNA

begins with a leader sequence: contains signals for RNA synthesis by RNA pol; its transcript contains signals that direct packaging of full-length plus strand copies of the genome with N protein to generate nucleocapsids

N, follwed by P/C/V, M, F, HN, and L genes

control transcription termination, polyadenylation, and reinitiation

a trailer sequence, which contains the promoter for genome replication and whose negative-strand transcript contains signals for genome packaging

• borders or genes
• regulate how many components are added

There is a short region that doesn't transcribe for anything

polymerase that is packaged in the virion makes + RNA, starting at 3' end of the genome RNA

RNA is made, capped, and polyadenylated by the L protein

alternative translational starts and by mRNA "editing"

• - Translation from multiple start sites created a nested set of proteins
• Editing occurs when RNA polymerase stutters, adding an extra G residue

• open reading frames
• translational start sites
• stuttering site

Transcription into +RNA via viral RNA polymerase as opposed to translation

• contains two to three gylcoproteins
• H
• F
• Matrix

responsible for binding to receptors on the surface and can bind to receptors on RBCs and hemagglutinate them Some can have neuraminidase activity

directs fusion

lies on inner surface of envelope

involved in virus assembly; serves as bridge between nucleocapsid and transmembrane envelope glycoproteins

the F1/F2 (fusion) protein undergoes a conformational change at neutral pH that allows insertion of the fusion peptide into the plasma membrane of the cell. =--> fusion of to membranes

contains a single envelope glycoprotein, responsible both for receptor binding and fusion activity

enter the cell by endocytosis and fusion with the endocytic membrane occurs at low pH, releasing the nucleocapsid into the cytoplasm

multiple translational start sites between the nt 81 and 203 

Four are in the same reading frame and ribosomes that initiate protein synthesis at these sites produce a nested set of proteins

• specific editing site
• P reading frame

the RNA polymerase to stutter and add one or more extra G residues within the stretch of 3 G's

• cofactor required for viral RNA synthesis carried out by the L protein
• binds to L and directs binding of L to the promoter

• required for formation of infectious virions
• also modulates activity of RNA polymerase

antagonizes the effects of interferon, and modulates activity of RNA pol

not normally required for replication of paramyxo; elimination of it reduces the virulence of Sendai virus; needed for virulence in mice

Once sufficinet N protein is made, genome rep begins

N protein levels control the switch from transcription to genome replication, whcih produces a full length positive strand, which is encapsidated by N. Full length negative strands are then made and encapsidated by N

assembled at the plasma membrane

fusion competent envelope proteins are present on the cell membrane, causng cells to fuse with neighboring cells, resulting in syncytia