viruses. egyptian stele (1580-1350 b.c) crippled priest
TRANSCRIPT
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Viruses
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Egyptian stele(1580-1350 B.C)Crippled priest
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Poxviruses(Poxviridae)
• The Pharaoh Ramses V died of smallpox (variola virus) in 1157 B.C.
• In 1520: 22 - 3.5 million Aztecs died
• Last case in Somalia on 26th October 1977
• Sept.11—variola virus as a bioterrorism weapon?
• Don’t confuse with chickenpox (varicella)
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VIRUSES• Virus = Latin for poison• Isolation of the first Virus
– Dmitri Iwanowski in 1892
–Tobacco mosaic virus which affects >150 plants world
wide stunted growth
–“filterable agent”
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VIRUSES, LIVING ORGANISMS?
• Life=A complex set of processes resulting from the actions of proteins specified by nucleic acids
• Viruses:–Inert outside host cells–Obligate intracellular parasites–Do not divide
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VIRION• A complete, fully developed viral
particle• Virions are the transmissible state of a
virus. Metabolically inert• Virions must be able to adhere and
allow entry into some host cell(s)• Also to survive outside of host cell
environment. • Some virions more hardy than others
(hepatitis virus A can withstand short periods of boiling; most virions are destroyed by this)
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VIRUS SIZE
• Most, 20 to 300 nm –(0.02 to 0.3 m)
• Filoviruses up to 14,000 nm–Exceptional
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STRUCTURE OF VIRUSES
• Only one type of nucleic acid (NA)–DNA or RNA
• NA enclosed by a protein coat
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Circular Linear
Segmented
Types of viral nucleic acids
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VIRAL CAPSOMERS
• Protein subunits, building blocks of the viral capsid
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STRUCTURE OF VIRUSES
• Capsid composed of repeating subunits - capsomers
• helical, icosahedral, complex • protection, attachment,
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ENVELOPED VIRUSES
• Envelope present–Part of host’s cell membrane
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Structure of Viruses
•Envelope derived from host membrane lipids and virus proteins •nuclear, plasma membrane by budding •necessary for attachment
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Capsid
Envelope
Nucleicacid
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NONENVELOPED OR NAKED VIRUSES
• Envelope absent• More resistant than
enveloped viruses
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• "Naked" viruses require host death so viruses can be released
• Enveloped viruses: are shed virus particles ; they shed by budding out, continued release from cell membrane
• Cell does not die (immediately), continues to serve as factory for virus assembly and release. Virus typically acquires a coating of host cell membrane, and will include virus-specific proteins. This is the "envelope"
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Examples of enveloped viruses include:
•Retrovirus, I.e. HIV
•Paramyxovirus, I.e. influenza
•Rhabdovirus, I.e. rabies
•Enveloped Herpes virus
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Nucleic acid
Capsid
Naked virus (no envelope)
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TYPES OF VIRUSES
• Animal viruses• Plant viruses• Bacteriophages (Virus that infects Bacteria)–Ex: Coliphage infect E.coli cells
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Types of Viral Infections
Oncogenic viruses
Herpes viruses
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VIRAL METABOLISM
• Multiply using the machinery of the host cell
• Have few or no enzymes
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HOST RANGE
• Species specific–Small pox virus, humans
• Broad host range–Rabies virus, mammals
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VIRAL SPIKES
• Carbohydrate/protein complexes embedded in the viral envelope
• Used as means of identification–Influenza virus, avian flue (H5N1)/Adenovirus
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Adenovirus spikesRespiratory Illness, Common Cold,
“Pink Eye”, Gastrointestinal Illness
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VIRAL MORPHOLOGY• Helical
–Cylindrical capsid with a helical structure
• Polyhedral–Icosahedral (20 triangular faces and 12 corners)
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Helical nucleocapsid
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RHABDOVIRUS
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POLYHEDRAL
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VIRAL MORPHOLOGY (cont.)
• Complex viruses–Structures attached to capsid
•Tail, tail fibers–Bacteriophages
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Bacteriophage
Tail
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POXVIRUS
Infections due to the poxviruses (members of the Poxviridae family) occur in humans and animals.
The orthopoxviruses include smallpox (variola), monkeypox, vaccinia, and cowpox viruses.
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CLASSIFICATION OF ANIMAL VIRUSES
• Type of nucleic acid–DNA or RNA–Single stranded (ss) or double stranded (ds)
• Presence of envelope
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CLASSIFICATION OF ANIMAL VIRUSES
• Strategy for Replication–Where do they replicate?
• Morphology–Structures
–Described by common Names
–Where is their niche? (Enteroviruses)
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Non-enveloped Enveloped
dsDNA AdenovirusPapovavirus
HerpesvirusPoxvirusHepadenavirus
ssDNA Parvovirus -
dsRNA Reovirus Retrovirus
ssRNA Picornavirus TogavirusFlavivirusCoronavirusRhabdovirus
Classification of viruses
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CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssDNA, nonenveloped–Parvovirus (Parvovirus B19 Fetal
Death, GI)• dsDNA, nonenveloped
–Adenovirus (Respiratory, GI)
–Papovavirus (Warts, Tumors)
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CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• dsDNA, enveloped–Poxvirus (Smallpox, Cowpox)
–Herpesvirus (Fever blisters, Chicken pox, Shingles, Mononucleosis)
–Hepadnavirus (Hepatitis B, Tumors)
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HERPESVIRUS
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CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssRNA, nonenveloped–Picornavirus (Polio, Common Cold,
GI)• dsRNA nonenveloped
–Reovirus (GI, Respiratory)• dsRNA enveloped
–Retrovirus (Tumors, AIDS)
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POLIOVIRUS
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Polivirus structure
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REOVIRUS
reo (for respiratory, enteric, and orphan, the latter meaning not associated with human disease)
Reoviruses are infectious agents of the virus family Reoviridae, transmitted by respiratory and fecal-oral routes. They are not major human pathogens
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RETROVIRUSThey are enveloped viruses, with
an RNA genome. The name is derived from the fact that the
virus particle contains an RNA-dependent DNA Polymerase
(Reverse transcriptase)
This enzyme converts the RNA genome into DNA, which then
integrates into the host chromosomal DNA. The reverse
transcriptase is highly error prone and rapid genetic variation
is a feature of this group
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CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssRNA, enveloped–Togavirus (Encephalitis) –Flavivirus (Dengue Fever,
Yellow Fever, West Nile Virus)
–Coronavirus (Common Cold)
–Rhabdovirus (Rabies)
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CORONAVIRUS
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CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssRNA, enveloped
–Filovirus (Ebola, Marburg) –Arenavirus (Hemorrhagic Fever)
–Paramyxovirus (Mumps)
–Orthomyxovirus (Influenza)
–Bunyavirus (Hantavirus)
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FILOVIRUS
Filovirus. Although very "hot" in the news, these viruses are very poorly characterized because of their extreme pathogenicity. They are class IV pathogens, meaning they can only be cultured in total containment facilities, of which there are only two in the U. S. They are thought to be enveloped viruses with - RNA genomes.
Marburg and Ebola virus
Appear in many different shapes (pleomorphic)
First ID in Germany/Yugoslavia from tissues of green monkeys who developed hemorrhagic fever
Filo = threadlike
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PART II
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GROWTH OF VIRUSES
• Bacteriophages–Bacterial cells
• Animal viruses–Animal cells
–Animals and embryos
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Growing Viruses•Animal Viruses
•A. Living Animals
•mice, rabbits, guinea pigs
•B. Chicken Embryos (Eggs)
•used to be most common method to grow viruses
•Still used to produce many vaccines (Flu Vaccine)
•C. Cell Cultures
•Most common method to grow viruses today
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PLAQUE ASSAY
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LIVING ANIMALS
• Diagnostic• Vaccine research• Expensive• Regulated
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NEWBORN MOUSE
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EMBRYONATED EGGS
• Diagnostic• Vaccine production• Inexpensive• Unregulated
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CHIKEN EMBRYO
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CHIKEN EMBRYO
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CHICKEN EMBRYO
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ANIMAL CELL CULTURES
• Derived from animals, or humans
• Culture in special medium• Infected cells show
cytopathic effect (CPE)
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Non-infectedmonkey cells
Infectedmonkey cells
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Multinucleated (giant) cellsinfected with reovirus
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INCLUSION BODIES POX VIRUS
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ANIMAL CELL CULTURES• Primary cell lines
–Tissues• Diploid cell lines
–Human embryos• Continuous cell lines
– Cancerous cells
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“...This lecture is dedicated to the memory of Mrs. Henrietta Lacks,
whose very cells,after her death,
have helped scientist all around the world to find
ways to alleviate suffering and prevent disease
among all of us, who are still here...”
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VIRAL IDENTIFICATION METHODS
• Electron microscopy• Serological
–Specific antibodies • Molecular biology
–Nucleic acid sequences
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VIRAL MULTIPLICATION
• Viral genes–Viral proteins–A few enzymes (if any) usually involved with viral nucleic acid replication
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VIRAL MULTIPLICATION (cont.)
• Infected cell provides:–Enzymes and machinery for viral nucleic acid and protein synthesis
–Energy
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BACTERIOPHAGE MULTIPLICATION
• Lytic cycle (lytic phages)–Lysis and death of host cell
• Lysogenic cycle (Lysogenic or temperate phages)–Host cell carries phage NA and divides normally
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LYSOGENIC (TEMPERATE) PHAGES
• Upon infection phage inserts its DNA into the host chromosome (prophage)
• Prophage genes may alter host cell characteristics by transduction
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TRANSDUCTION
• Generalized–Phage picks up, randomly, fragments of host DNA instead of phage’s DNA
–May transfer any gene
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TRANSDUCTION (cont.)
• Specialized–Phage DNA that has been integrated to host DNA is exised along with a few adjacent host genes
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LYSOGENIC PHAGES (cont.)
• Toxins produced by:–Corynebacterium diphteriae–Streptococcus pyogenes–Clostridium botulinum
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VIRAL MULTIPLICATION
• Attachment• Penetration• Biosynthesis• Maturation• Release
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ONCOGENIC VIRUSES
• Viral nucleic acid gets integrated into host genome
• Alteration of cellular growth genes
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LATENT VIRAL INFECTIONS
• Virus/host equilibrium–Herpes viruses
•Cold sores
•Shingles (chicken pox)
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SLOW VIRAL INFECTIONS
• Virus builds up gradually• Usually fatal
–Subacute sclerosing panencephalitis
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PRIONS• Protein• Undetectable nucleic acid?, a
bacterium?–Neurological diseases–Creutzfeldt-Jacob disease–Mad cow disease
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HOST CELL DEFENSES
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INTERFERON (IFN)
• Antiviral proteins (AVP) produced by virus-infected cells
• Interfere with viral multiplication
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INTERFERON (cont.)
• Host-cell specific• Not virus specific• Short lived• No effect on infected cells
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INTERFERON TYPES
• Alpha (IFN• Beta (IFN• Gamma (IFN)
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INTERFERON ACTIVITY
• IFNs diffuse and gain entrance to non-infected neighboring cells
• Induce synthesis of antiviral proteins
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INTERFERON ACTIVITY • Antiviral proteins:
–Destruction of viral mRNA
–Inhibit translation of viral mRNA
–Inhibit polypeptide elongation
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RABBITS AND MYXOMATOSIS
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AUSTRALIA
• Introduced Rabbits First arrived in 1778 from Europe
• Spread 125 Km/year• Soon became a pest
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MYXOMATOSIS
• Caused by a poxvirus• Mild infection in Australian
native rabbits• Fatal infection in the
introduced European rabbits
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TRANSMISSION OF MYXOMATOSIS
• Mosquito• Flea• Direct contact
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MYXOMA VIRUS IN AUSTRALIA
• Introduced in the Summer 1950-1951
• By 1956 the European rabbit population dropped 90%
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MYXOMA VIRUS IN AUSTRALIA (cont.)
• As time went on:• Rabbit population began to
recover• Appearance of less virulent
viruses• Appearance of more resistant
rabbits