Viruses

1. Viruses Are they living or not?

2. Brief History of virus discovery • Are agents that can’t be seen with an ordinary light microscope • Are agents that pass through filters that can trap even the smallest bacteria • The question that arose was are these agents toxins or poisons? • The Latin word for poisons is viruses

3. Basic Virology • What is a virus? • Is it living or nonliving? • How are they different from other “living” organisms? • Submicroscopic 18-350 nm in size (10-9 M) • Can only be “seen” with an electron microscope • Obligate intracellular parasites • Viruses have no genes that encode the proteins that function as the metabolic machinery for energy generation • Viruses have no genes that encode the proteins that function as the metabolic machinery for protein synthesis • Viruses may or may not contain the genes that encode enzymes involved in nucleic acid synthesis

4. Basic Virology • Biochemically • Have RNA or DNA, not both • Have no small ions or polysaccharides (sugars) • May (enveloped viruses) or may not (naked viruses) contain lipids

5. Basic Virology

6. Basic Virology • Growth curves of bacteria and viruses are very different Viral growth curve Bacterial growth curve

7. Differences in growth curves: • Virus particles are produced from the assembly of pre-formed components: other organisms grow from an increase in the integrated sum of their components and reproduce by cell division. • Viruses don’t “grow” or undergo division

8. Basic Virology • What is the basic structure of a virus? • Nucleic acid of RNA or DNA – is the genetic information for the virus • Single (SS) or double stranded (DS) • Linear, circular, or nicked • Unsegmented or segmented • If SS RNA, may be of the plus (+) or the minus (-) sense • + RNA– genomic RNA can serve as mRNA and be directly translated into protein • - RNA – genomic RNA cannot serve as mRNA and cannot be translated directly into protein

9. Basic Virology

10. Basic Virology • Protein outer coat – is called the capsid • The capsid is composed of individual subunits called capsomers • What is the function of the capsid? • Protects the delicate inner nucleic acid from harsh environmental conditions • May be involved in attachment to host cells • There are two basic capsid structures • Icosahedral • Helical

11. Basic Virology Icosahedral Structure

12. Basic Virology Helical structure

13. Basic Virology • Viruses that contain only the viral nucleic acid and the capsid are called naked viruses • Some viruses have an outer lipid layer called an envelope • The envelope is derived from host cell membranes • For viruses that use the plasma membrane as their envelope, the envelope is acquired as the virus exits the host cell via a process called budding • Virally encoded proteins in the envelope play a major role in the viral life cycle. • Proteins in the viral envelope are involved in attachment to host cells. • Proteins in the viral envelope mediate fusion of the virus envelope with host cell membrane during the entry of the virus into the host cell.

14. Basic Virology • Diagram of an enveloped virus (HIV):

15. Basic Virology - budding

16. Basic Virology • What is required for a virus to successfully infect and replicate in a host cell? • In order for a virus to successfully infect a host cell, the cell must contain the receptor that the virus binds to in the process of initiating an infection. • The part of the virus that binds to the receptor is called the ligand. • The ligand is on the capsid of naked viruses and on the envelope of enveloped viruses. • gp 120 (the ligand) on HIV binds to CD4 (receptor) and CXCR4 (co-receptor) on T lymphocytes or CCR5 (co-receptor) on macrophages

17. Basic Virology

18. Basic Virology • In order for a virus to successfully replicate in a host cell, the host cell must not only contain the receptor for the virus, it must also have the cellular machinery that the virus needs for replication. • The host range of a virus is the spectrum of host cells that the virus can successfully infect and replicate in. • If the virus successfully replicates in the host cell, the infection is productive and the host cell is said to be permissive for the virus.

19. Basic Virology • If the cell lacks something required for viral replication, the infection is abortive or non-productive and the host cell is considered to be non-permissive for the virus. • What are the basic features of the viral life cycle? • Attachment or adsorption– ligand on virus binds to a receptor on a host cell • Penetration – virus gets inside the host cell • Penetration of naked viruses usually involves either: • Receptor mediated endocytosis or • Formation of a pore in the host cell plasma membrane through which the nucleic acid and possibly associated viral proteins enter the cytoplasm

20. Basic Virology • Penetration of enveloped viruses occurs through a fusion event between the viral envelope and a host cell membrane. • Uncoating – separation of capsid and nucleic acid in preparation of viral transcription and nucleic acid replication (attachment and penetration may occur simultaneously)

21. Basic Virology • Biosynthesis – viral proteins are made and viral nucleic acid is replicated • RNA viruses must bring in their own enzyme(s) for transcribing their mRNAs and replicating their genome. • This is because neither prokaryotic cells nor eukaryotic cells contain enzymes that can use RNA as a template to make a complementary copy of RNA. • Therefore, most RNA viruses replicate entirely within the cytoplasm.

22. Basic Virology • DNA containing viruses can either use the host enzymes to transcribe their mRNAs and replicate their genomes, or they may bring in their own enzymes for these processes • Retroviruses are unique RNA viruses in that they bring in an enzyme called reverse transcriptase (RT). • RT makes a double stranded DNA copy of the viral RNA genome. • This DNA then moves to the nucleus where it is incorporated into the DNA of the host cell. • It is only after this occurs that the viral genes are transcribed and translated into protein products.

23. Basic Virology • Assembly or maturation – All of the viral components assemble into new viruses. • This does not occur until a sufficient number of viral proteins are made and viral genomes are replicated • Release – newly made viruses exit the host by lysis or budding

24. Basic Virology

25. Basic Virology • How are viruses classified? • The most commonly used classification scheme is the Baltimore scheme. • This scheme is based on the relationship between the viral genome and the mRNA used for translation during expression of the viral genome:

26. Baltimore Classification of Viruses

27. Basic Virology • Effects of the virus on the host cell – even though you can’t see the virus, you can see the effects that the virus has on the host cell • Death of the cell – often occurs on release of the virus • Cytopathic effects– are visible effects on the host cell caused by viral replication • Cancer • Requires that the virus integrates all or part of its genome into the host cell DNA

28. Overview of viral infections • Viral diseases of the skin • Warts • Caused by human papilloma virus (double stranded DNA) • Spread by direct contact • Treated with acids or cryotherapy • Smallpox (variola) • Caused by variola major (mortality >20%) and minor (mortality < 1%) (double stranded DNA) • Transmitted by respiratory route • Virus moves from respiratory tract to the bloodstream to the skin to cause a pustular rash • Leaves disfiguring scars

29. Smallpox lesions

30. Overview of viral infections • Other symptoms include fever, malaise, severe backache and abdominal pain • Vaccination has successfully eradicated this disease • Problem – use in bioterrorism • Chickenpox and shingles • Caused by varicella-zoster (a herpes virus - double stranded DNA) • Infection is through the respiratory route • Incubation is ~ 2 weeks, but the infected individual is contagious at this stage • Virus localizes in the skin to cause a vesicular rash with vesicles that fill with pus, rupture, and form scabs • After chickenpox the virus remains latent in nerve cells and can be reactivated later in life tocause shingles

31. Overview of viral infections • Shingles is characterized by severe pain due to inflammation of the nerve branches of the cutaneous sensory nerves around one side of the trunk. • A vaccine to prevent chickenpox is now available

32. Chicken pox and shingles

33. Overview of viral infections • Measles (rubeola) • Caused by a paramyxovirus (single stranded – sense RNA) • Is highly contagious • Spread by the respiratory route • Incubation 10-12 days • Symptoms are similar to the common cold plus a papular rash (small, raised spots) • Koplik spots (red patches with central white specks) in the oral cavity are diagnostic

34. Overview of viral infections • Severe complications include encephalitis, pneumonia, ear infections, and even death • May later cause subacute sclerosing panencephalitis with progressive nerve destruction and death • A vaccine is available (part of the MMR – Measles, Mumps, and Rubella) • We should be able to eradicate this virus since man is the only known host

35. Measles (rubeola)

36. Overview of viral infections • German measles (rubella) • Caused by a togavirus (single stranded + sense RNA) • Transmitted via the respiratory route • Symptoms include a slight fever and a rash of small red spots. • Infection during the first trimester of pregnancycan lead to birth defects (deafness, eye cataracts, heart defects, mental retardation) or death of the fetus • Vaccination via MMR

37. German measles (rubella)

38. Overview of viral infections • Cold sores • Caused by herpes simplex virus (HSV), type I (double stranded DNA) • Characterized by lesions of the oral mucous membranes • Following the initial infection, the virus may remain latent in the nerves • Physical or emotional stress may cause a reactivation of the latent infection • Viral diseases of the eye • Corneal lesions caused by HSV, type I can lead to blindness or CNS invasion

39. HSV I infections

40. Overview of viral infections • Viral diseases of the respiratory tract • The common cold • Caused mainly by rhinoviruses (single stranded + sense RNA) and coronaviruses (single stranded + sense RNA) • >200 different types of viruses can cause the common cold! • Spread by respiratory secretions on the hands • Symptoms include sneezing, nasal discharge, and congestion • Influenza • Caused by orthomyxoviruses (segmented, single stranded – sense RNA viruses)

41. Overview of viral infections • Transmitted via respiratory secretions • Symptoms include fever, chills, headache, and general muscle aches • These organisms are continually changing their antigenic structure by shift and drift making it difficult to develop effective vaccines • Shift occurs with genetic recombination or gene reassortment • Drift occurs by mutations • Viral diseases of the central nervous system • Meningitis or encephalitis

42. Overview of viral infections • These are infections of the membranes that cover the brain and spinal cord or of the brain itself • Many different viruses can cause meningitis and encephalitis • Organisms that enter through the blood need to cross the blood-brain barrier to cause disease. • Other organisms move along peripheral nerves to the CNS • Viral meningitis is often called aseptic meningitis because no bacteria or fungi can be cultivated from the CSF

43. Overview of viral infections • Poliomyelitis (polio) • Caused by a picornavirus (small single stranded+ sense RNA) • There are three different serotypes of poliovirus • Transmission occurs via the gastrointestinal tract after ingestion of fecal contaminated water • Symptoms include fever, sore throat, and headache • In 1-2% of the cases (mainly in adults) the virus penetrates the capillary walls and enters the CNS where it it multiplies in the motor nerve cells eventually killing them and causing paralysis • Two vaccines have been used • Salk – virus inactivated by formalin

44. Overview of viral infections • Sabin – live, attenuated virus ( recently reactivation problems have resulted in the discontinuation of the use of this vaccine) • Rabies • Caused by a bullet-shaped rhabdovirus (single stranded – sense RNA) • Transmission is via the saliva of a rabid (rabies infected) animal • Virus travels along the peripheral nerves to the CNS where it causes encephalitis • Symptoms include painful spasms of the muscles of the mouth and pharynx when swallowing liquids (hydrophobia) • Treatment is with rabies immune globulin followed by active immunization

45. Rabies

46. Overview of viral infections • Viral diseases of the cardiovascular system • Myocarditis – inflammation of the heart muscle • Caused by many different organisms, but is commonly caused by Coxsackieviruses (single stranded + sense RNA) • Infection occurs via the respiratory route or via the gastrointestinal tract • The organism gains access to the heart via the bloodstream or the lymphatics

47. Overview of viral infections • Infectious mononucleosis • Caused by Epstein-Barr virus (a herpes virus – double stranded DNA) • Transmission is via saliva and hence the disease is often called the kissing disease • Symptoms include fever, sore throat, swollen lymph nodes, and general weakness • Like all herpes virus infections, after the primary infection the virus remains latent, this time in B lymphocytes

48. Overview of viral infections • The virus has been linked to threehuman cancers • Hodgkins disease • Burkit’s lymphoma • Nasopharyngeal carcinoma

49. Burkitt’s lymphoma

50. Overview of viral infections • Viral hemorrhagic fevers • Caused by several different types of virus • Ebola virus causes this type of disease • Are transmitted from human to human • Have a high mortality rate from hemorrhaging and shock