Transcript virus - West Campus | Pima Community College, Tucson, Arizona

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 mm)
• 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
Types of viral nucleic acids
Circular
Linear
Segmented
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
Nucleic
acid
Capsid
Envelope
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
Naked virus
(no envelope)
Capsid
Nucleic
acid
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 spikes
Respiratory 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
Tail
Bacteriophage
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)
Classification of viruses
Non-enveloped Enveloped
dsDNA
Adenovirus
Papovavirus
Herpesvirus
Poxvirus
Hepadenavirus
ssDNA
Parvovirus
-
dsRNA
Reovirus
Retrovirus
ssRNA
Picornavirus
Togavirus
Flavivirus
Coronavirus
Rhabdovirus
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
Reoviruses are infectious agents of the virus family Reoviridae,
transmitted by respiratory and fecal-oral routes. They are not major
human pathogens
reo (for respiratory, enteric, and orphan, the latter meaning not associated
with human disease)
RETROVIRUS
They are enveloped viruses, with
an RNA genome. The name is
derived from the fact that the
virus particle contains an RNAdependent 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
Marburg and Ebola virus
Filo = threadlike
Appear in many different
shapes (pleomorphic)
First ID in
Germany/Yugoslavia from
tissues of green monkeys who
developed hemorrhagic fever
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.
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)
Infected
monkey cells
Non-infected
monkey cells
Multinucleated (giant) cells
infected 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 (a-IFN)
• Beta (b-IFN)
• Gamma (g-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