Transcript Viral Diseases - De Anza College

Viruses
Not Composed of Cells
Characteristics
• Obligate intracellular parasites
• Single type of nucleic acid
• Protein coat
• Envelope
Two Forms
• Extracellular form
• Intracellular form
Host Range
• Can infect many hosts
• Determined by attachment to host cell
– cell wall, flagella/fimbriae
• Receptor sites, or plasma membrane in
animal cells
Structure
• Nucleic acid-core
• Either DNA or RNA, not both
• Follows central dogma of molecular
biology
– Genetic info flows from NA to protein
Structure
• Protein coat-capsid
• Envelope in some virions
– May or may not have spikes-glycoproteins
Envelope
• Acquire membrane when budding or pass
through membranes
• Advantages of lipid membrane
• Lose infectivity when envelope destroyed
Envelope
• Host’s phospholipids & viral proteins
• Disadvantage -damaged easily
• Without envelope- naked viruses
– More resistant to chemicals/ disinfectants
Enzymes
• Required early in infection process
• Bacterial virus or bacteriophage
– lysozyme
• Lysis of cell and release of virions
Enzymes
• Some have own NA polymerase
• RNA polymerase in some RNA virions
• Reverse transcriptase in retro viruses
– RNA dependent DNA polymerase
• Neuramidases-release of virions
Morphology
• Helical
• Polyhedral- shape of icosohedron-20 sides
• Enveloped- usually spherical
Morphology
• Complex viruses
– combination of helical and icosohedral
– bacterial viruses-head and tail
– poxviruses- several coats of protein
Growth of Bacteriophage
• Grow in suspensions of bacteria or in
bacteria cultures on plate
• Plaque method for counting
Growth of Animal Viruses
• Living animals
• Embryonated eggs-influenza
• Cell cultures-continuous lines
CPE Cytopathic Effect
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Visible effect of viruses on cells
Stop multiplication of cells
Lysosomes release enzymes
Inclusion bodies
SyncytiumInterferons-
CPE
• Mark infected cells for destruction by
immune system
• Transformation-abnormal cells
Multiplication of Bacteriophage
• Lytic cycle: produces virions
• T-even phages, virulent phages, on E. coli
– ds DNA for over 100 genes-head
– tail sheath-retracts
– DNA moves from head into host
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Lytic Cycle
• Attachment stage (adsorption)
– attachment site on virus with complementary
receptor on bacteria cell wall
– use fibers at end of tail as attachment sites
– may attach to flagella or fimbriae
Penetration
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Injects DNA
Tail releases enzyme lysozyme
Tail core driven through cell wall
Tail reaches cell membrane
Capsid remains outside: uncoating
Biosynthesis
• In cytoplasm
• Host protein synthesis is stopped
• Uses host nucleotides and enzymes to
synthesis copies of phage DNA
Biosynthesis
• Synthesis of phage capsid proteins
• Uses host ribosomes and amino acids for
translation
Maturation
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Assemble into mature phages
Head assembled and packed with DNA
Phage tails assembled from plates, sheaths,
Each head attached to tail
Then fibers are attached
Release
• Lysis of PM, cell breaks open
• Virulent (lytic) phages
One Step Growth Curve
• One step growth curve
• Always present are mutant bacteria with
altered receptors
Lysogenic Cycle
• Temperate phages do not always under go
lytic cycle:
• Lysogeny• Phage NA incorporated into the host NA
• Lambda phage in E. coli
– Integrates into bacterial chromosome
– Prophage
Lysogenic Cycle
• Prophage replicated along with host DNA
• On rare event- can lead to popping out of
phage DNA
Lysogenic Conversion
• Alteration of characteristics of bacteria
• Cells are immune to reinfection by same
phage
• Not immune to infection by different phage
Phage Conversion
• Medical significance of conversion
• C. diphtheriae and C. botulinum
• Without prophage do not cause disease
• Strep with prophage can cause scarlet fever
Specialized Transduction
  Mediated by lysogenic phage ( only temperate
virions)
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 DNA on either side of prophage can be picked
up
  Phage lambda picks up gene for galactose
fermentation-gal from host
  Carry this gene to new host which is gal
negative
Multiplication of Animal Viruses
• Attachment
– receptor sites on animal cells - proteins and
glycoproteins of PM
– sites are distributed all over surface of virus
• Spikes or capsid
Penetration
• Trigger endocytosis-folding inward of
PM-vesicle
• Enveloped viruses also can fuse with PM
– Fusion protein facilitates this
– Releases capsid via endocytosis
Uncoating-Removal of Capsid
• Varies with virus
• Separation of NA and protein coat
– lysosomal enzymes inside vesicles
• Some enzymes in host cytoplasm
Biosynthesis of DNA viruses
• DNA viruses replicate DNA in nucleus of host
• Synthesize proteins in cytoplasm
• Early transcription- for enzymes & proteins
needed for viral DNA replication
• Late transcription-capsid & structural proteins
Maturation
• Assembly of virus
– Takes place in nucleus
– Proteins transported via ER into nucleus
• Released from host cell
– Budding
– Lysis
Biosynthesis of RNA Viruses
• Multiply in host cell’s cytoplasm
• Picornavirus-polio, ss RNA,
• RNA is a sense strand or positive since it
acts as mRNA
• Early translation-2 proteins
– Inhibits host cell synthesis of RNA & protein
– Produces RNA-dependent RNA polymerase
Biosynthesis of SS RNA Virus
  Synthesizes another strand of RNAantisense strand or negative strand
– Serves as template for all + strands
• Late transcription and translation -proteins
for capsids
Rhabdoviruses
• Rabies, bullet shaped
• Contains a single minus strand and RNA
dependent RNA polymerase
– makes + strands from minus strand
• + strand serves as mRNA for new viral
RNA and for proteins
Maturation and Release
• Assemble capsids spontaneously
• Enveloped viruses
– proteins in envelope encoded by viral genes
– envelope wraps around capsid -budding
• Lipids and CH2O encoded by host cell
• Noneveloped viruses released via rupture
Retrovirus
• HIV
– Positive strand RNA virus
– Own RNA polymerase
– RNA dependent DNA polymerase
– Reverse transcriptase
– RNA to DNA
Provirus
• Viral DNA incorporated into host DNA –
provirus
• Never comes out of host chromosome
• Protected from host’s immune system and
antiviral drugs
Retrovirus Replication
• Provirus may remain in latent state replicating
with host DNA OR
• Provirus may be expressed and produces new
viruses
Consequences of Virus Infection
• Lytic infection: destruction of host cell
– Acute infection-influenza
• Persistent infection : slow release of virions
– Budding without lyzing cell
Consequences of Virus Infection
• Latent infections: delay between infection
and lytic events
• Transformation: change in cell
Herpes Viruses
• Large, enveloped, latent
• Herpes type 1 and 2
– Cold sores, genital and neonatal herpes
– Varicella zoster- chickenpox, and
shingles
• EBV-mononucleosis
Herpes Viruses
• CMV
– Salivary gland virus-acute febrile illness, birth
defects
• Roseolovirus (6)
– Infants with rash and fever
• HHV-7 rashes in infants
• HHV-8 Kaposi’s sarcoma
Transformation
• Normal cells become tumor cells
– Benign and malignant
• Oncogene-cancer gene
Oncogenes
• Genes always turned on
– Continuous cell division
• Activated to abnormal functioning by
chemicals, radiation and viruses
• Loss of control of cell cycle
– Result in formation of tumors
Oncogenic viruses
• 10- 20% of cancers known to be virus
induced
• Oncogenic viruses incorporate into host
DNA
– Cells lack contact inhibition
DNA Oncogenic Viruses
• EBV- herpes virus, causes 2 human cancers
– Burkitt’s lymphoma ( rare affecting children in Africa)
– Nasopharyngeal cancer is worldwide
• 90% of population carry latent stage of EBV in
lymphocytes
• Hepatitis B virus has casual role in liver cancer
• Papilloma virus- can cause cervical & penile
cancer-vaccine
RNA Viruses
• Human T cell leukemia viruses
Prions
• Proteinaceous infectious particle
– Lacks nucleic acid
• Degenerative changes in brain-large
vacuoles
– Dementia, wasting, & loss of motor control
Prions-CJD
• Modified forms of normal cellular proteins
• Cause disease by converting normal protein
into abnormal forms
CJD
• Transmission
– Ingestion of contaminated food
– Sporadic cases
– Contaminated surgical instruments
• Neural electrodes or forceps etc.
Influenza
• 8 segments of RNA as genome: minus
strands
• Protein capsid
• Envelope with projections (virus can change
these so it survives each year)
Spikes
• H spikes -hemagglutinin (binds to host
receptors)
– Recognize cells and attach
• 100 N spikes -neuraminidase
– Release virus from infected cell
Influenza
• Spread by droplets-use regular mask
• HA bind to ciliated respiratory cells
• Envelope fuses with PM and enters cells
S&S
• Release of cytokines
• Incubation period- 1-3 days, spread day
before symptoms
• Ill 7-10 days
Recovery
• Spontaneous
• Secondary infections
• Death
Strains of A Viruses
• Strains H1,H2, H3; N1 and N2
• Antigenic shift-responsible for outbreaks
– Reassortment
Antigenic Shift (continued)
• Genetic reassortment
• 2 viral strains infect the same animal/human
• Swine can be infected by both human &
avian strains-mixing vessel
Antigenic Shift (continued)
• New virions released from swine
• Must have a full complement of the RNA
segments to be infective
• May occur every 10 years or more
Antigenic Drift
• Minor annual variations in genetic make-up
of HA or NA
• RNA enzymes lack proofreading capability
H1N1 Virus
• Originated in swine
• Virulence similar to seasonal influenza viruses
• Humans have little or no immunity
Healthcare Worker PPE
• CAL OSHA requirement for H1N1
• Wear N95 mask
–Must be fit-tested for mask
–Wear a visor over mask
–Wear gown & gloves
Vaccination
• Get vaccinated yearly
• Seasonal vaccine
–2 types of strains of A: H1N1 &
H3N2
–1 B strain
• H1N1 available
Antiviral Drugs for H1N1
• Sensitive to neuraminidase inhibitors
–Tamiflu
–Relenza
• Prevents virus from leaving cell
• Benefit if started within 48 hours of
illness onset
Influenza Pandemics in
the
20th Century
Years
Flu
Virus
Deaths
1918-1919
“Spanish”
Type A (H1N1)
675,000 US
1957-1958
“Asian”
Type A (H2N2)
70,000 US
1968-1969
“Hong Kong”
Type A (H3N2)
34,000 US
2009
“Swine”
Type A (H1N1)
8000 US
Pandemic Influenza
• Pandemic influenza virus
– A new influenza A subtype can infect humans
– Causes serious illness
– Spreads easily from human-to-human
H5N1 is a likely candidate, but is not a
pandemic virus yet
H1N1 is a pandemic virus
AIDS
• Final stage of a long infection with HIV
– Attacks immune system
– T helper cells and macrophages
2 Types
• HIV 1-99% of all global cases
• HIV 2 discovered in West Africa
– Reduced virulence
– Causes milder disease
Structure of HIV
• 2 positive strands of RNA
• 2 identical strands of RNA enzyme- reverse
transcriptase
– Copies RNA into DNA
• Envelope with spikes termed gp120glycoprotein of 120,000 mw
Pathogenicity
• Spikes allow attachment to CD4 receptors on
host cells
• Coreceptors on T helper cells needed also for
attachment
Fusion Protein
• Fuses CM with viral envelope
– Nucleocapsid enters cell
– Uncoated to release enzyme and RNA
Life Cycle
• RNA plus strands used for template only
• Viral DNA incorporates into host DNA
 Integrase enzyme (viral) joins viral DNA
with cellular DNA
• May be latent or cause disease
Protease
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Another enzyme in viral core
Budding virus is not mature yet
Proteins in core are in one long strand
Must be cut by protease then virus is
infectious
Mutations
• Rapid antigenic mutations
• Mutations at every position in genome
many times each day
AIDS
• Progression to AIDS
– based on T cell population
• Progression from HIV to AIDS is about 10
years
HIV Transmission
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Contact with infected body fluids
BloodSemen Heterosexual sex fastest growing risk factor
Drug use and multiple partners
Mother to baby, breast feeding
Treatment: Highly Active Anti
Retrovirus Therapy
• Nucleoside analogs-AZT etc. inhibit reverse
transcriptase
• Proteases- enzyme that cuts proteins into pieces
reassembled into coat of new HIV particles
• Integrase inhibitors- enzyme that incorporates
viral DNA into DNA of host
• Fusion inhibitors