1. Living or nonliving? Biological?
Viruses
Living or nonliving?
Biological?

2. 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”

3. What is a Virus? Different from “living” MOs & cells
Submicroscopic 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)

4. Animal Viruses

5. 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

6. Virus Nucleic Acid Single (ss) or double stranded (ds)
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

7. Virus Genome

8. Virus Protein Capsomer - individual protein subunits of capsid
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

9. Virus Capsid Two basic capsid structures:
Icosahedral (spherical polygon)
Helical (elongated rod)

10. 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)

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. Classification of Virus
One most commonly used virus classification is Baltimore scheme
Based on relationship between viral genome and its mRNA needed for translation

18. 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

19. 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)

20. 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)

21. 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

22. Smallpox Variola virus (dsDNA) Transmitted by respiratory route
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?

23. 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)

24. 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

25. Measles Rubeola virus (paramyxovirus, ssRNA) Highly contagious
Spread by respiratory route
Incubation 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

26. 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

27. 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

28. 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

29. Ocular Infections HSV, type I Corneal lesions
Can lead to blindness or CNS invasion

30. Upper & Lower Respiratory Tract Infections
Common cold
Influenza

31. 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)

32. 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

33. Viremia & Sepsis Infectious mononucleosis - lymphocytes
Blood and lymph systems
Myocarditis – inflammation of heart muscle
Infectious mononucleosis - lymphocytes
Viral hemorrhagic fever – rash, fever

34. Myocarditis Commonly caused by Coxsackievirus (ss RNA)
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

35. 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

36. 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

37. 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)

38. 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

39. 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

40. GI Infections Mumps (parotitis) – salivary gland
Hepatitis - inflammation of the liver
Viral gastroenteritis – intestine

41. Mumps Mumps virus (Paramyxovirus, ssRNA)
Transmission via salivary secretions and portal of entry is respiratory tract
Incubation 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

42. “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

43. “Serum” Hepatitis Hepatitis B virus (dsDNA) Hepatitis C virus (ssRNA)
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

44. 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

45. STD
Genital herpes
Genital warts

46. 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

47. 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

48. 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