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Spring, 2004 Lecture Outline

3/4 MINUS-STRAND VIRUSES

RHABDOVIRIDAE, PARAMYXOVIRIDAE, ORTHOMYXOVIRIDAE

 

[-] strand RNA virus introduction:

strategy difference in [-] strand vs. [+] strand viruses must make mRNA before translation

Rhabdoviridae

bullet helical

Paramxyoviridae

spherical, non-segmented genome

Orthomyxoviridae

spherical, segmented genome

Filoviridae

flexible filaments

Arenaviridae

spherical, ambisense segmented genome

Bunyaviridae

spherical, segmented genome


Rhabdoviridae: simplest of minus-strand grp

prototype: vesicular stomatitis virus- cattle, mild Dz

structure: lipid rich envelope c peplomers

ssRNA minus strand in helical nucleocapsid
-UUUUUUUGUCUUCGU 3'} will form panhandle structure
-AAAAAAACAGAACCA 5'

transcription: VSV RNA 4 x 106 d -> 5 mRNAs codes for 5 proteins

transcription req. leader seq., begins at 3'; reads "stop-start"
signals- produces 5 mRNA c methylated caps & poly(A)

replication: appears to use same enzyme as transcription- forms

full-length [+] strand intermediate & progeny minus strands

assembly:

M protein attaches to inside of fused lipid-G protein complex at cell surface N, L, NS proteins assoc. c M
helical nucleocapsid pushes against lipid bilayer, forming bud


Rabies: Pasteur developed vaccine from "fixed" virus

Negri discovered unique inclusion bodies in nerve cells of infected animals & humans- diagnostic of Dz

all strains isolated world wide are of single immunological type

transmission & path; epidemiology; vaccines & treatment

 

Introduction to Paramyxoviridae & Orthomyxoviridae:

myxovirus term denotes viral affinity for glycoproteins
two major peplomer fxns- hemagglutinin & neuraminidase

difference:

orthomyxo- has segmented genome [imagine minichromosomes] paramyxo- nonsegmented genome


Paramyxoviruses:

genus Paramyxovirus: mumps, parainfluenza- human (some paras- other animals); Newcastle Dz (NDV)- chicken

genus Morbillivirus: measles- human; distemper- dog; rinderpest- cattle

genus Pneumovirus: RSV- human; BRSV- cattle

structure: pleomorphic- spheres to filaments, 150-300 nm diameter

helical nucleocapsid- protects vs. ribonuclease
neuraminidase- cleaves sialic acid from oligosaccharides
fusion protein- appears to aid viral-cell fusion p attachment

transcription & replication: similar to rhabdovirus; no seq. homology

conclusion- both families descended from common ancestor


Orthomyxoviruses: influenza (flu) family- many unique features

types: serological differences of nucleocapsids
many subtypes & strains- internally same, surface protein differences

structure: shape- pleomorphic: 100 nm spheres, filaments several 1000 nm

majority protein- M forms shell around nucleocapsid c/ envelope
2 types of peplomers: hemagglutinin & neuraminidase
RNA: 6 x 106 d total; divided- 8 different RNAs, each for different gene

Ag shift: reassortment of segments -> new serotypes responsible for epidemics
Ag drift: less dramatic, due to point mutations

transcription:

occurs in host nucleus instead of cytoplasm like most RNA viruses; 1st transcription- in core

progression of translational events occur more in cytoplasm


defective interfering particles:

interference 1st noted in flu viruses: von Magnus particles
lack some, esp. largest, RNA molecules
blocks replication of normal particles

Influenza pathology


Paramyxoviral diseases: replication phases vary greatly, incubation periods vary

parainfluenza, measles, mumps, RSV


Prevention & control: role of natural exposure & vaccines

 

Next week:

Filoviridae, Arenaviridae, & Bunyaviridae- see CRC, ch 7 & appropriate parts of Wagner, including ch 16, & on-line

Midterm 1: Review notes, reading, diagrams, study guide- from beginning through [+] strand ssRNA viruses

 

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 Updated 1/25/04 by thatcher@sonoma.edu