Lecture 14: Viruses

Originates from Latin meaning: poison or toxin

Features of viruses
- Simple acellular structure
- DNA or RNA (not both)
- Obligate intracellular parasites – requires a host cell for reproduction
o There are bacteria that have DNA and RNA (ex. Chlamydia, Rickettsia)
o How do you grow chlamydia in a lab – infect into rabbit testicle, harvest, remove testicle,
lyse cells, obtain replicated chlamydia

History of Viruses
1885-1900
Chamberland:
- developed a porcelain filter that eliminated bacteria
Iwanowski and Beijerinck:
- found that filtered extracts from tobacco could transmit disease to another plant even after
filtering through pores known to retain even the smallest bacterium
- something in that filtrate can cause disease (not bacteria)
- Discovered the tobacco mosaic virus
- Beginning of virology

1900-1935
Some viruses linked to the development of cancer
Ellerman and Bang  chicken leukemia virus
Peyton Rous  sarcoma virus (Nobel prize)
- Purified virus and causes disease in chickens (fulfilled Koch’s postulates)
- Sarcoma: connective tissue cancer

Some viruses found that infected bacteria

Twort  infectious agents that lysed bacteria (discovered bacteriophages)
D’Heurelle  bacteriophage plaque assay

Virus composition
Stanley, Bowen and Pirie
- Tobacco Mosaic Virus mostly protein and contains nucleic acid

Basic Structure of Viruses

- 10 nm – 0.4 µm (400 nm)
- Few to several hundred genes
- Has a nucleocapsid core (DNA/RNA protein coat that binds nucleic acid)
- Lipid membrane (envelope)
- Virally encoded enzymes

Virus: replicative intracellular form

Virion: extracellular infectious particle, non-replicating

How does a virus differ from a plasmid (textbook!!!!)

 capsid: protein coat(s)
protomers: protein monomers that self-associate to form the final capsid
assembly of viral capsid proteins: held together by non-covalent bonds
- Capsids only comprised of one or few polypeptides to save space on
small genome

Capsids
Symmetry
- Helical: protomers form a helix which wraps around nucleic acids
o Ex. Tobacco Mosaic Virus
- Icosahedral: 20-sided polygon with 12 vertices
o Ex. Adenovirus
 Most efficient way to enclose a space
- Complex
o Ex. Vaccinia virus (pleiomorphic structure), bacteriophage (combination of capsid
symmetries)

Viral Envelope: bilayer that surrounds the nucleocapsid

- Only found in some viruses
o Most animal
o Some plant
o Few bacteriophages
- Lipid comes from plasma membrane: ER, Golgi, nuclear membrane of
HOST

- Lipid and carbohydrates derived from host

- Proteins encoded by virus, amino acids from host
- Viruses without lipid envelopes: naked viruses
o Influences susceptibility to disinfectants
- Spike proteins encoded by virus using amino acids from host

- Spike proteins are immunogenic

o Elicit immune response
- Influenza virus – spike proteins encode
o Hemagglutinin: crosslinks and clumps red blood cells
o Neuraminidase: enzyme that clears host sialic acid to release virions upon budding

Viral budding from Host Cell

- Viral proteins inserted into host plasma membrane
- Nucleocapsid binds to inner surface of host
plasma membrane
- Viral proteins collect at site of viral contact
- Host proteins excluded
- Plasma membrane buds, forms viral envelope
- Virion released

Viral nucleic acids: DNA or RNA, not both

Genome size of viruses: 4000-5000 nts
Few to 100+ proteins encoded by viral genome
Overlapping genes and no introns – save space on small genome

RNA viruses
- Two types of RNA strands
- + or sense strand = +RNA = mRNA
o Can immediately be transmitted to viral proteins
- - or antisense strand = -RNA
o Complementary + strand must be made before viral proteins translated

Picornavirus: small RNA virus

Poliovirus

Paramyxovirus: causes mumps,

measles
750k deaths/year

Orthomyxoviruses
Influenza

Reoviruses: respiratory and GI

viruses

HIV: human immunodeficiency virus,

can lead to AIDs
Goes through DNA intermediate

HIV
- Virus only transcribed one, DNA integrated into host genome
- Movie

Replicating Viral RNA

- For +, -, +/- RNA viruses: RNA polymerase needed
- For retroviruses (HIV): reverse transcriptase needed to copy +RNA to DNA

Viral taxonomy – International Committee for the Taxonomy of Viruses

- A panel of international experts regulate virus naming
- How many are there? All organisms can be infected
o 2000 diff viruses (probable more)

Naming a Virus
Suffix Used Example
Order -virales Mononegavirales
Family -viridae Paramyxoviridae
Subfamily -virinae Paramyxovirinae
Genus -virus Rubulavirus
Type Species -virus Mumps virus

Baltimore System
- Developed by David Baltimore (MIT)
- Nobel Prize – Reverse Transcriptase
 - Compliments and simplifies ICTV system
Classification based on nature of viral genome and how the virus makes mRNA
7 different groups of viruses based on Baltimore Classification System

Cultivating a Virus
- Viruses cannot be grown in media  require host cell
Animal viruses
- Suitable host animal
o Often used but can be difficult if virus has narrow host range
o Especially with human specific viruses
- Embryonic chicken eggs
o Fertilize eggs
o Viruses injected into specific parts
- Cultured animal cells
o Monolayer of cells derived from specific tissues
 (lung, kidney, intestine)

Pocks: virally induced lesions

Plaque: a zone of clearing caused by virally induced lysis
Cytopathic effects: observable changes to cells due to viral replication; changes depned on the
virus and cell type used

To grow bacteriophages
- Plate lawn of susceptible bacterial cells
- Playues form from bacteriophage induced lysis
- Diff phages create diff plaque types

Plant viruses
- Whole plant
o In nature, plant viruses transmitted by insects  apply virus to plant surface
- Plant tissue culture
o Used to cultivate viruses in specific cell types