viruses viruses living or nonliving? biological?
TRANSCRIPT
VirusesViruses VirusesViruses
Living or nonliving?Living or nonliving?
Biological?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? 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 non-productive 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 (bullet-
shaped 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