Download Viruses – Invisible Invaders, Amazing Allies

Viruses
Living or nonliving?
Biological?
Virus Discovery
 Agents not seen with light microscope
 Pass through filters that trap bacteria
(<0.2µm)
 Are these toxins or poisons?
 ”Virus” - Latin for “poison”
What is a Virus?
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Different from “living” MOs & cells
Submicroscopic 18-350 nm
Seen with electron microscope
Obligate intracellular parasites
 No genes for metabolic machinery and energy
 ±Genes for nucleic acid synthesis
 Biochemically
 RNA or DNA, not both
 No small ions, polysaccharides (sugars)
 ±Virus modifided lipid membranes from host cell
(enveloped viruses or naked viruses)
Animal Viruses
Virus Replication Kinetics
 Growth curve of bacteria and virus very
different
 Virus - from assembly of pre-formed
components
 MOs - from increase in sum of components,
reproduce by cell division
 Viruses don’t “grow” or undergo division
Bacterial growth curve
Viral growth curve
Virus Nucleic Acid
 RNA or DNA – genetic information
 Single (ss) or double stranded (ds)
 Linear, circular, or nicked
 Unsegmented (single molecule) or
segmented (two or more moleclues)
 ssRNA may be plus (+) or minus (-) sense
 (+)RNA genome can serve as mRNA and directly
translated into protein
 (-)RNA genome cannot serve as mRNA and
cannot be translated directly into protein
Virus Genome
Virus Protein
 Capsid – “coat”, outer structure made up of
protein
 Capsomer - individual protein subunits of
capsid
 Function of capsid:
 Protect nucleic acid from harsh environment
 Involved in attachment to host cell
Virus Capsid
 Two basic capsid structures:
 Icosahedral (spherical polygon)
 Helical (elongated rod)
Virus Envelope
 Naked virus - only
nucleic acid and
capsid
 Enveloped virus outer lipid
membrane layer
 Envelope from host
cell membrane plus
virus glycoprotein
 Enveloped human
immunodeficiency
virus (HIV)
Virus Exits Cell By Budding
 Enveloped virus
acquire cell plasma
membrane as exits
host cell via budding
 Virus glycoprotein
(ligand) in envelope
play role in
attachment to host
cell (receptor)
 Mediate fusion of
virus envelope with cell
membrane during virus
entry into host cell
Virus Infection and Attachment
 Host must contain
cell receptor that
virus binds to in
initiating infection
 Virus ligand binds to
cell receptor
 Ligand on capsid of
naked virus and on
outside of envelope
virus
 gp 120 (the ligand) on
HIV binds to CD4
(receptor) on T
lymphocyte or CCR5
on macrophage
Virus Replication In A Host Cell
 Host cell must also have cellular metabolic
machinery that virus needs for replication
 Host range of virus is spectrum of host
cells that virus can infect and replicate in
 If virus successfully replicates in host cell,
infection productive and host cell is
permissive for virus
 If cell lacks something required for viral
replication, infection abortive or nonproductive and host cell is non-permissive
for virus
Virus Replication Cycle
 Attachment - ligand on virus binds to
receptor on host cell
 Penetration - virus gets inside host cell
 Naked virus: either receptor mediated
endocytosis or formation of pore
 Enveloped virus: through fusion event
 Uncoating - separation of capsid and
release of nucleic acid into cell cytoplasm
or nucleus; preparation of viral
transcription and nucleic acid replication
 Biosynthesis - viral proteins and viral
nucleic acid replicated
Virus Biosynthesis
 RNA viruses - bring in own enzymes for
transcribing mRNA and replicating their genome
 Cells do not contain enzymes for RNA as a template
 Most RNA viruses replicate in cytoplasm
 DNA viruses - either use host enzymes or bring
in own enzymes to transcribe mRNA and
replicate genome
 Retroviruses - unique RNA virus bring in enzyme
called reverse transcriptase (RT)
 RT makes a dsDNA copy of viral ssRNA genome
 DNA then moves to nucleus where incorporated into
cell DNA, then viral genes transcribe mRNA and
translated
Virus Replication Cycle
 Assembly - viral
components
self-assemble
into new
viruses, occurs
when sufficient
number of viral
proteins and
viral genomes
made
 Release - newly
made virus exit
host cell by
lysis or budding
Classification of Virus
 One most commonly used virus classification is
Baltimore scheme
 Based on relationship between viral genome and its
mRNA needed for translation
Virus Infection and
Pathology of Host Cell
 Even though can’t see virus, can see effects
that virus has on host cell
 Death of cell – often occurs on release of virus
 Cytopathic effects – visible effects on cell
caused by viral replication (plaques, rounded,
syncytia)
 Cancer (cell transformation) – loss of cell
growth control; require virus integrates all or
part of genome into cell DNA
Overview of Virus Infectious
Diseases By Organ Systems
 Skin and Soft Tissue Infections
 Ocular Infections
 Upper and Lower Respiratory Tract
Infections (URTI, LRTI)
 Viremia and Sepsis
 Infections of Central Nervous System
(CNS)
 Gastrointestinal Infections (GI)
 Sexually Transmitted Diseases (STD)
Skin and Soft Tissue
Infections
 Warts (Papilloma virus)
 Smallpox (Variola virus)
 Chickenpox/Shingles (Varicella/Zoster
virus)
 Measles (Rubeola virus)
 German measles (Rubella virus)
 Cold sores (Herpes Simplex virus)
Warts
 Human papilloma virus (dsDNA)
 Spread by direct contact
 Benign tumors with abnormal
uncontrolled growth but stops after
period of time
 Some infections result in cell
transformation and malignant tumors
 Treated with acids or cryotherapy
Smallpox
 Variola virus (dsDNA)
 Variola major (mortality >20%)
 Variola minor (mortality < 1%)
 Transmitted by respiratory route
 Virus moves from respiratory tract, bloodstream,
skin to cause pustular rash that leaves scars
 Symptoms include fever, malaise, severe backache
and abdominal pain
 WHO vaccination program successfully
eradicated disease
 Use in bioterrorism?
Chickenpox and Shingles
 Varicella-zoster virus (herpesvirus, dsDNA)
 Infection via respiratory route
 Incubation ~ 2 weeks, but infected
individual contagious at this stage
 Virus localizes in skin to cause vesicular
rash with vesicles that fill with pus,
rupture, and form scabs
 After chickenpox, virus remains latent in
nerve cells and can be reactivated later in
life to cause shingles (zoster)
Chickenpox and Shingles
 Shingles characterized by severe pain due to
inflammation of sensory nerves around one
side of nerve trunk
 Vaccine to prevent chickenpox now available
Measles
 Rubeola virus
(paramyxovirus, ssRNA)
 Highly contagious
 Spread by respiratory
route
 Incubation 10-12 days
 Symptoms similar to
common cold plus
papular rash (small,
raised spots)
 Koplik spots (red
patches with central
white specks) in the oral
cavity are diagnostic
Measles
 Severe complications include
encephalitis, pneumonia, ear infections,
and even death
 May later cause subacute sclerosing
panencephalitis with progressive nerve
destruction and death
 Vaccine available (part of MMR –
Measles, Mumps, and Rubella)
 Often fatal infection of infants in
developing countries due to underlying
malnutrition with >1 million deaths/year
German Measles
 Rubella virus (Togavirus,
ssRNA)
 Three day measles
 Transmitted via
respiratory route
 Symptoms include slight
fever and rash of small
red spots
 Infection during first
trimester of pregnancy
can lead to birth defects
(deafness, eye cataracts,
heart defects, mental
retardation) or death of
the fetus
 Vaccination via MMR
Cold Sores
 Herpes Simplex virus (HSV), type I (dsDNA)
 Characterized by lesions of oral mucous
membranes
 Following initial infection, virus remains latent in
nerves
 Physical or emotional stress may cause reactivation of
latent infection
Ocular Infections
 HSV, type I
 Corneal lesions
 Can lead to blindness or CNS invasion
Upper & Lower Respiratory
Tract Infections
 Common cold
 Influenza
Common Cold
 Rhinoviruses (ssRNA) and Coronaviruses
(ssRNA)
 >200 different types of rhinoviruses can
cause common cold!
 Spread by respiratory secretions on hands
and inhalation
 Symptoms include sneezing, nasal
discharge, and congestion
 Emerging pathogen is SARS-CoV (Severe
acute respiratory syndrome-Coronavirus)
Influenza
 Influenza virus (Orthomyxovirus,
segmented, ssRNA)
 Transmitted via respiratory secretion
 Symptoms include fever, chills, headache,
and general muscle aches
 Viruses are continually changing antigenic
structure by “drift” and “shift” making it
difficult to develop host immunity and
effective vaccine
 Drift occurs by RNA mutation
 Shift occurs by genetic recombination or gene
reassortment during dual infection of a host
Viremia & Sepsis
 Blood and lymph systems
 Myocarditis – inflammation of heart
muscle
 Infectious mononucleosis - lymphocytes
 Viral hemorrhagic fever – rash, fever
Myocarditis
 Caused by many different MOs
 Commonly caused by Coxsackievirus (ss
RNA)
 Via respiratory route or GI tract
 Gains access to heart via bloodstream or
lymphatics
Infectious Mononucleosis
 Epstein-Barr virus
(Herpesvirus, dsDNA)
 Transmission via saliva,
“kissing disease”
 Symptoms include fever,
sore throat, swollen
lymph nodes, general
weakness
 Like all herpesvirus,
after primary infection it
remains latent, in B
lymphocytes
 Linked to three cancers
 Hodgkins disease
 Burkitt’s lymphoma
 Nasopharyngeal carcinoma
Infections of CNS
 Meningitis and encephalitis
 Infection of membrane that cover brain and spinal
cord and infection of brain
 By many different viruses
 Virus may enter through blood, and need to cross
“blood-brain barrier”
 Other virus move along peripheral nerve into CNS
 Viral meningitis often called “aseptic meningitis”
because no bacteria or fungi found in CSF
 Poliomyelitis
 Rabies
Poliomyelitis
 Poliovirus (Picornavirus, ssRNA)
 Three poliovirus serotypes
 Transmission occurs via GI tract after ingestion
of fecal contaminated water
 Symptoms include fever, sore throat, and
headache
 In 1-2% of cases virus penetrates capillary walls
and enters CNS where it multiplies in motor
nerve cells eventually killing them and causing
paralysis
 Two vaccines used:
 Salk – wild type virus inactivated by formalin
 Sabin – oral, live, attenuated virus ( recent reactivation
to virulence resulted in use of inactivated vaccine for
first dose followed by two oral doses for infant
vaccination)
Rabies
 Rabies virus (bulletshaped Rhabdovirus,
ssRNA)
 Transmission via saliva of
rabid animal
 Virus travels along
peripheral nerve to CNS
where it causes encephalitis
 Symptoms include painful
spasms of muscles of mouth
and pharynx when
swallowing liquids
(hydrophobia)
 Treatment is with rabies
immune globulin followed by
active immunization
Viral Hemorrhagic Fever
 Caused by several different viruses
 Ebola virus causes this type of disease
 Transmitted from animal to human, then
human to human
 Infects and destroys blood vessels
 High mortality rate from hemorrhaging and
shock
 Natural animal host is unknown
GI Infections
 Mumps (parotitis) – salivary gland
 Hepatitis - inflammation of the liver
 Viral gastroenteritis – intestine
Mumps
 Mumps virus (Paramyxovirus,
ssRNA)
 Transmission via salivary
secretions and portal of
entry is respiratory tract
 Incubation 16-18 days –
during this time virus moves
from respiratory tract,
bloodstream, to parotid
(salivary) gland and teste in
males
 Symptoms include swelling,
fever, painful swallowing,
occasionally sterility
 Vaccination is via MMR
“Infectious” Hepatitis
 Hepatitis A virus (ssRNA)
 Transmitted via fecal-oral route
 Symptoms include anorexia, malaise,
nausea, diarrhea, abdominal discomfort,
fever and chills for 2-21 days
 Two-thirds of infected individuals have
jaundice indicative of liver damage
 Recovery complete with no chronic
disease
“Serum” Hepatitis
 Hepatitis B virus (dsDNA)
 Transmitted via body secretions (blood, saliva,
STD) and needle sharing among drug abusers
 Incubation 4-26 weeks
 Symptoms range from subclinical to severe
fever and headache with jaundice
 Most recover completely, but 10% chronic
carriers with high incidence of liver disease and
cancer
 Recombinant vaccine is available
 Hepatitis C virus (ssRNA)
 Disease and transmission similar to HBV
 No vaccine available
Viral Gastroenteritis
 In children, most commonly caused by
rotavirus (dsRNA) or adenovirus (ds
DNA)
 Symptoms include fever, diarrhea,
vomiting
 In developing countries, high mortality
among infants resulting in >1 million
deaths/year due to underlying
malnutrition and fluid loss
STD
 Genital herpes
 Genital warts
Genital Herpes
 Herpes simplex virus (HSV) type
II (dsDNA)
 Incubation ~ 1 week
 Asymptomatic or symptoms of
painful vesicular lesions
containing infectious fluid
 Becomes latent in nerve cells and
may be reactivated to cause
same lesions in primary infection
 Can cross the placenta to infect
fetus leading to mental
retardation, defective sight and
hearing
 Fetus can also be infected during
delivery, therefore all women
positive for this virus routinely
deliver by C-section
Genital Warts
 Human papilloma
viruses (dsDNA)
 Benign warts and
tumors
 Some strains cause
malignant tumors,
cervical cancer
 Vaccine (Gardasil)
for these virus
strains to prevent
cervical cancer
Subviral Particles: Prions
 Proteinaceous infectious particle
 No nucleic acid
 Self-replicating by misfolding of normal cellular
protein
 Formerly called “slow viral infections”
 Neurological disease in mammals, transmissible
spongiform encephalopathy (TSE), eventual death
 Kuru and Creutzfeldt-Jakob disease
 Scapie in sheep
 Bovine spongiform encephalopathy (Mad cow disease)
 Chronic wasting disease in deer and elk