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