Post on 20-Mar-2016
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Viruses
Egyptian stele(1580-1350 B.C)Crippled priest
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)
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”
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
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)
VIRUS SIZE• Most, 20 to 300 nm
–(0.02 to 0.3 m)• Filoviruses up to 14,000 nm
–Exceptional
STRUCTURE OF VIRUSES• Only one type of nucleic acid
(NA)–DNA or RNA
• NA enclosed by a protein coat
Circular Linear
Segmented
Types of viral nucleic acids
VIRAL CAPSOMERS• Protein
subunits, building blocks of the viral capsid
STRUCTURE OF VIRUSES
• Capsid composed of repeating subunits - capsomers
• helical, icosahedral, complex • protection, attachment,
ENVELOPED VIRUSES• Envelope present
–Part of host’s cell membrane
Structure of Viruses
•Envelope derived from host membrane lipids and virus proteins •nuclear, plasma membrane by budding •necessary for attachment
Capsid
Envelope
Nucleicacid
NONENVELOPED OR NAKED VIRUSES
• Envelope absent• More resistant than enveloped viruses
• "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"
Examples of enveloped viruses include:
•Retrovirus, I.e. HIV
•Paramyxovirus, I.e. influenza
•Rhabdovirus, I.e. rabies
•Enveloped Herpes virus
Nucleic acid
Capsid
Naked virus (no envelope)
TYPES OF VIRUSES• Animal viruses• Plant viruses• Bacteriophages (Virus that
infects Bacteria)–Ex: Coliphage infect E.coli cells
Types of Viral Infections
Oncogenic viruses
Herpes viruses
VIRAL METABOLISM• Multiply using the machinery
of the host cell• Have few or no enzymes
HOST RANGE• Species specific
–Small pox virus, humans• Broad host range
–Rabies virus, mammals
VIRAL SPIKES• Carbohydrate/protein complexes
embedded in the viral envelope• Used as means of identification
–Influenza virus, avian flue (H5N1)/Adenovirus
Adenovirus spikesRespiratory Illness, Common Cold,
“Pink Eye”, Gastrointestinal Illness
VIRAL MORPHOLOGY• Helical
–Cylindrical capsid with a helical structure
• Polyhedral–Icosahedral (20 triangular faces and 12 corners)
Helical nucleocapsid
RHABDOVIRUS
POLYHEDRAL
VIRAL MORPHOLOGY (cont.)
• Complex viruses–Structures attached to capsid
•Tail, tail fibers–Bacteriophages
Bacteriophage
Tail
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.
CLASSIFICATION OF ANIMAL VIRUSES
• Type of nucleic acid–DNA or RNA–Single stranded (ss) or double stranded (ds)
• Presence of envelope
CLASSIFICATION OF ANIMAL VIRUSES
• Strategy for Replication–Where do they replicate?
• Morphology–Structures–Described by common Names–Where is their niche?
(Enteroviruses)
Non-enveloped EnvelopeddsDNA Adenovirus
PapovavirusHerpesvirusPoxvirusHepadenavirus
ssDNA Parvovirus -dsRNA Reovirus RetrovirusssRNA Picornavirus Togavirus
FlavivirusCoronavirusRhabdovirus
Classification of viruses
CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssDNA, nonenveloped–Parvovirus (Parvovirus B19 Fetal
Death, GI)• dsDNA, nonenveloped
–Adenovirus (Respiratory, GI)
–Papovavirus (Warts, Tumors)
CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• dsDNA, enveloped–Poxvirus (Smallpox, Cowpox)
–Herpesvirus (Fever blisters, Chicken pox, Shingles, Mononucleosis)
–Hepadnavirus (Hepatitis B, Tumors)
HERPESVIRUS
CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssRNA, nonenveloped–Picornavirus (Polio, Common Cold,
GI)• dsRNA nonenveloped
–Reovirus (GI, Respiratory)• dsRNA enveloped
–Retrovirus (Tumors, AIDS)
POLIOVIRUS
Polivirus structure
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
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
CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssRNA, enveloped–Togavirus (Encephalitis) –Flavivirus (Dengue Fever,
Yellow Fever, West Nile Virus)
–Coronavirus (Common Cold)
–Rhabdovirus (Rabies)
CORONAVIRUS
CLASSIFICATION OF ANIMAL VIRUSES (cont.)
• ssRNA, enveloped–Filovirus (Ebola, Marburg) –Arenavirus (Hemorrhagic Fever)
–Paramyxovirus (Mumps)
–Orthomyxovirus (Influenza)
–Bunyavirus (Hantavirus)
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
PART II
GROWTH OF VIRUSES• Bacteriophages
–Bacterial cells• Animal viruses
–Animal cells–Animals and embryos
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
PLAQUE ASSAY
LIVING ANIMALS• Diagnostic• Vaccine research• Expensive• Regulated
NEWBORN MOUSE
EMBRYONATED EGGS• Diagnostic• Vaccine production• Inexpensive• Unregulated
CHIKEN EMBRYO
CHIKEN EMBRYO
CHICKEN EMBRYO
ANIMAL CELL CULTURES• Derived from animals, or
humans• Culture in special medium• Infected cells show
cytopathic effect (CPE)
Non-infectedmonkey cells
Infectedmonkey cells
Multinucleated (giant) cellsinfected with reovirus
INCLUSION BODIES POX VIRUS
ANIMAL CELL CULTURES• Primary cell lines
–Tissues• Diploid cell lines
–Human embryos• Continuous cell lines
– Cancerous cells
“...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...”
VIRAL IDENTIFICATION METHODS
• Electron microscopy• Serological
–Specific antibodies • Molecular biology
–Nucleic acid sequences
VIRAL MULTIPLICATION• Viral genes
–Viral proteins–A few enzymes (if any) usually involved with viral nucleic acid replication
VIRAL MULTIPLICATION (cont.)
• Infected cell provides:–Enzymes and machinery for viral nucleic acid and protein synthesis
–Energy
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
LYSOGENIC (TEMPERATE) PHAGES
• Upon infection phage inserts its DNA into the host chromosome (prophage)
• Prophage genes may alter host cell characteristics by transduction
TRANSDUCTION• Generalized
–Phage picks up, randomly, fragments of host DNA instead of phage’s DNA
–May transfer any gene
TRANSDUCTION (cont.)• Specialized
–Phage DNA that has been integrated to host DNA is exised along with a few adjacent host genes
LYSOGENIC PHAGES (cont.)• Toxins produced by:
–Corynebacterium diphteriae–Streptococcus pyogenes–Clostridium botulinum
VIRAL MULTIPLICATION• Attachment• Penetration• Biosynthesis• Maturation• Release
ONCOGENIC VIRUSES• Viral nucleic acid gets
integrated into host genome• Alteration of cellular growth
genes
LATENT VIRAL INFECTIONS
• Virus/host equilibrium–Herpes viruses
•Cold sores•Shingles (chicken pox)
SLOW VIRAL INFECTIONS• Virus builds up gradually• Usually fatal
–Subacute sclerosing panencephalitis
PRIONS• Protein• Undetectable nucleic acid?, a
bacterium?–Neurological diseases–Creutzfeldt-Jacob disease–Mad cow disease
HOST CELL DEFENSES
INTERFERON (IFN)• Antiviral proteins (AVP)
produced by virus-infected cells
• Interfere with viral multiplication
INTERFERON (cont.)• Host-cell specific• Not virus specific• Short lived• No effect on infected cells
INTERFERON TYPES• Alpha (IFN• Beta (IFN• Gamma (IFN)
INTERFERON ACTIVITY• IFNs diffuse and gain
entrance to non-infected neighboring cells
• Induce synthesis of antiviral proteins
INTERFERON ACTIVITY • Antiviral proteins:
–Destruction of viral mRNA–Inhibit translation of viral mRNA
–Inhibit polypeptide elongation
RABBITS AND MYXOMATOSIS
AUSTRALIA
• Introduced Rabbits First arrived in 1778 from Europe
• Spread 125 Km/year• Soon became a pest
MYXOMATOSIS• Caused by a poxvirus• Mild infection in Australian
native rabbits• Fatal infection in the
introduced European rabbits
TRANSMISSION OF MYXOMATOSIS
• Mosquito• Flea• Direct contact
MYXOMA VIRUS IN AUSTRALIA
• Introduced in the Summer 1950-1951
• By 1956 the European rabbit population dropped 90%
MYXOMA VIRUS IN AUSTRALIA (cont.)
• As time went on:• Rabbit population began to
recover• Appearance of less virulent
viruses• Appearance of more resistant
rabbits