Viruses and Viral Diseases

1. Viruses and Viral Diseases

2. Size range most <0.2 μm requires electron microscope Virion fully formed virus able to establish an infection General Structure of Viruses

4. General Structure of Viruses • Capsids • All viruses possess • Constructed from identical subunits called capsomers • made of protein • nucleoscapsid • Capsid + nucleic acid

5. Three main structural types: helical Continuous helix of capsomers forming a cylindrical nucleocapsid icosahedral 20-sided with 12 corners vary in the number of capsomers Some are enveloped Complex General Structure of Viruses

6. Icosahedral Helical

7. General Structure of Viruses • Viral envelope • mostly animal viruses • acquired when virus leaves host cell • Protects the nucleic acid when the virion is outside the host cell • spikes • exposed proteins on the outside of the envelope • essential for attachment of the virus to the host cell • Naked • composed only of a nucleocapsid • Enveloped • surrounded by an envelope

8. Complex viruses: atypical viruses Poxviruses lack typical capsid covered by dense layer of lipoproteins Bacteriophages Virus that infects and replicates within bacterial cells General Structure of Viruses

9. Viruses have host range and tissue specificity Host range refers to what organisms the virus can infect depends on capsid structure Many viruses infect certain cell or tissue types within the host (tissue tropism) Viral targets

10. Nucleic acids • Viral genome • either DNA or RNA but never both • Carries genes necessary to invade host cell • then redirect cell’s activity to make new viruses • Number of genes varies for each type of virus • few to hundreds

11. DNA viruses usually double stranded (ds) may be single stranded (ss) circular or linear Nucleic Acids

12. DNA viruses causing human disease: enveloped DNA viruses nonenveloped DNA viruses nonenveloped ssDNA viruses DNA Viruses

13. Nucleic Acids • RNA viruses • usually single stranded • may be double stranded • Segmented versus nonsegmented • positive-sense RNA • ssRNA genomes ready for immediate translation • negative-sense RNA • ssRNA genomes that must be converted into proper form

14. RNA Viruses • Assigned families based on envelope, capsid, and nature of RNA genome

15. Viruses….a comparison • Most DNA viruses are budded off the nucleus • Most RNA viruses multiply in & released from the cytoplasm • Most DNA & a few RNA viruses can become permanent resident of the host cell • Several viruses can cross the placenta & cause developmental disturbances

16. What about Viral classification?? • Acellular • Completely different way of classifying • Will discuss in viral section….

17. Naming Viruses • 3 Orders • Order name end in –virales • Herpesvirales • 63 Families • Family name ends in -viridae • Herpesviridae • 263 genera • Genus name ends in –virus • Simplexvirus, Herpes simplex virus I (HSV-I)

18. Naming Viruses • Family – Herpesviridae • Genus – Varicellovirus • Common name – chickenpox virus • Disease - chickenpox

19. Modes of Viral Multiplication

20. Animal virus replication • attach to host plasma membrane via spikes on the capsid or envelope

21. Genome Replication • DNA viruses • RNA viruses • ds • Two complementary paired nucleic acids • ss • Unpaired nucleic acids • Reverse transcribing viruses

22. Use host cell’s synthesizing machinery ds DNA releases its DNA then: Enters nucleus Is transcribed Viral mRNA translated and proteins enter nucleus Viral DNA replicated in nucleus Viral DNA and proteins assembled CAN insert itself into host DNA 1. DNA Viruses

23. 2. RNA Viruses • Genetic information encoded in RNA • Use own enzymes to copy their genomes • Can be: • (-) genome and must be converted before translation • (-) that can be converted to DNA or dsRNA • (+) genome ready to be translated into proteins

24. Penetration and uncoating of viral RNA Directly translated on host cell ribosomes into viral proteins (-) genome synthesized to produce for final assembly (-) template used to make (+) replicates RNA strands assembled (+) genome ready to be translated into proteins

25. Synthesize DNA using their ssRNA genome as a template Reverse transcriptase Packaged with each viral particle Synthesizes ssDNA from their template Directs formation of complementary strand of above =dsDNA virus strand Enters nucleus integrated into host genome We then make more ssRNA 3. Reverse Transcribing Viruses

26. Some DNA viruses and retroviruses insert their genome into the host chromosome as a provirus Retroviruses use reverse transcriptase to transcribe their RNA to DNA It can then be inserted into the host chromosome Some Animal Viruses Can Exist as Proviruses

27. adsorption penetration replication assembly maturation release 6 Steps in Viral Replication

28. 1. Adsorption and Host Range • Virus coincidentally collides with a susceptible host cell • adsorbs specifically to receptor sites on the cell membrane • Attachment • host range • Spectrum of cells a virus can infect • hepatitis B – human liver cells • poliovirus – primate intestinal and nerve cells • Rabies – various cells of many mammals

29. 2. Penetration/Uncoating • Flexible cell membrane penetrated by the whole virus (or its nucleic acid) by: • endocytosis • entire virus engulfed and enclosed in a vacuole or vesicle • fusion • envelope merges directly with membrane • Results in nucleocapsid’s entry into cytoplasm

30. 3. Replication • Varies depending on whether the virus is a DNA or RNA virus • DNA viruses generally are replicated and assembled in the nucleus • RNA viruses generally are replicated and assembled in the cytoplasm

31. 4. & 5. Assembly and Maturation • Mature viruses made from various parts • Capsid laid down first • Enveloped • Insert viral spikes

32. 6. Release • Assembled viruses leave host cell in one of two ways: • budding • exocytosis • nucleocapsid binds to membrane which pinches off and sheds the viruses gradually • cell is not immediately destroyed • lysis • nonenveloped and complex viruses released when cell dies and ruptures

33. Damage to Host Cell Cytopathic effects - virus-induced damage to cells • Changes in size & shape • Cytoplasmic inclusion bodies • Nuclear inclusion bodies • Cells fuse to form multinucleated cells • Cell lysis • Alter DNA • Transform cells into cancerous cells

35. Techniques in Cultivating and Identifying Animal Viruses • Obligate intracellular parasites require appropriate cells to replicate • In vitro • In vivo • Methods used: • cell (tissue) cultures • bird embryos • live animal inoculation

36. Cell (tissue) cultures cultured cells grow in sheets that support viral replication permit observation for cytopathic effect Techniques in Cultivating and Identifying Animal Viruses

37. Bird embryos incubating egg is an ideal system virus is injected through the shell Techniques in Cultivating and Identifying Animal Viruses

38. live animal inoculation occasionally used when necessary Techniques in Cultivating and Identifying Animal Viruses

39. Pathogenic DNA Viruses

40. Poxviruses Produce eruptive skin pustules called pocks or pox Largest and most complex animal viruses largest genome of all viruses dsDNA variola – cause of smallpox vaccinia – closely related virus used in vaccines monkeypox cowpox

42. Smallpox first disease to be eliminated by vaccination exposure through inhalation or skin contact infection associated with fever, malaise, prostration, & a rash Variola major highly virulent, caused toxemia, shock, & intravascular coagulation Variola minor less virulent routine vaccination ended in US in 1972 reintroduced in 2002

43. Molluscum Contagiosum caused by unclassified poxvirus primarily an infection of children transmitted by direct contact and fomites AIDS patients suffer atypical form attacks the skin of the face forms tumorlike growths Treatment freezing, electric cautery, chemical agents

44. The Herpesviruses All members show latency and cause recurrent infection more severe with advancing age, cancer chemotherapy, or other conditions that compromise the immune defenses

45. Herpesviridae large Family; 8 infect humans HSV-1 HSV-2 VZV EBV CMV HHV-6 HHV-7 HHV-8

46. Epidemiology of Herpes Simplex Viruses:HSV-1 & 2 Transmission direct exposure to secretions containing the virus active lesions most significant source genital herpes can be transmitted in the absence of lesions HSV multiplies in sensory neurons, moves to ganglia HSV-1 enters 5th cranial nerve HSV-2 enters lumbosacral spinal nerve trunk ganglia

47. Epidemiology of Herpes Simplex Viruses Recurrent infection triggered by various stimuli fever, UV radiation, stress, mechanical injury Newly formed viruses migrate to body surface produce a local skin or membrane lesion

48. Type 1 Herpes Simplex (HSV – 1) Herpes labialis fever blisters, cold sores most common recurrent HSV-1 infection vesicles occur on mucocutaneous junction of lips or adjacent skin itching and tingling prior to vesicle formation lesion crusts over in 2-3 days and heals Herpetic gingivostomatitis infection of oropharynx in young children fever, sore throat, swollen lymph nodes Herpetic keratitis ocular herpes

49. Type 2 Herpes Simplex (HSV – 2) Genital herpes herpes genitalia starts with malaise, anorexia, fever, and bilateral swelling and tenderness in the groin clusters of sensitive vesicles on the genitalia, perineum, and buttocks urethritis, painful urination Recurrent bouts usually less severe triggered by menstruation, stress, and concurrent bacterial infection

50. Herpes of the Newborn HSV-1 and HSV-2 Potentially fatal in the neonate and fetus Infant contaminated by mother before or during birth hand transmission by mother to infant Infection of mouth, skin, eyes, CNS Preventative screening of pregnant women delivery by C-section if outbreak at the time of birth