1. C H A P T E R © 2014 Pearson Education, Inc. PowerPoint ® Lecture Presentations prepared by Mindy Miller-Kittrell, North Carolina State University Pathogenic DNA Viruses 24

2. © 2014 Pearson Education, Inc. DNA Viruses DNA viruses causing human disease are grouped into seven families based on several factors: Type of DNA they contain dsDNA ssDNA Hepadnaviridae contain both dsDNA and ssDNA The presence or absence of an envelope Size The host cells they attack

3. © 2014 Pearson Education, Inc. Poxviridae Double-stranded DNA viruses Have complex capsids and envelopes Second largest viruses Infect many mammals Most animal poxviruses are species specific Unable to infect humans because cannot attach to human cells Infection occurs primarily through the inhalation of viruses Close contact is necessary for infection by poxviruses Smallpox and molluscum contagiosum the main diseases of humans Some diseases of animals can be transmitted to humans All poxviruses produce lesions that progress through stages

4. © 2014 Pearson Education, Inc. Poxviridae Smallpox In the genus Orthopoxvirus Commonly known as variola Exists in two forms Variola major Causes severe disease with a 20% mortality rate Variola minor Causes milder disease Variola infects internal organs, causing fever, malaise, and delirium The virus moves via the blood to the skin, where it produces pox Scars result on the skin, especially on the face

5. © 2014 Pearson Education, Inc. Figure 24.3 Smallpox lesions.

6. © 2014 Pearson Education, Inc. Poxviridae Smallpox Smallpox is the first human disease to be eradicated Several factors enabled the eradication of smallpox Inexpensive, stable, and effective vaccine No animal reservoirs Obvious symptoms allow for quick diagnosis and quarantine Lack of asymptomatic cases Virus is only spread via close contact Stocks of the virus are maintained in laboratories in the U.S. and Russia

7. © 2014 Pearson Education, Inc. Poxviridae Molluscum Contagiosum Caused by Molluscipoxvirus Skin disease characterized by smooth, waxy papules Typically on face, trunk, and external genitalia Spread by contact among infected individuals Children Sexually active individuals AIDS patients Treatment involves removing the infected nodules People with normal immunity heal without treatment Sexual abstinence prevents genital form of the disease

8. © 2014 Pearson Education, Inc. Figure 24.4 Lesions of molluscum contagiosum.

9. © 2014 Pearson Education, Inc. Poxviridae Other Poxvirus Infections Poxvirus infections also occur in animals Transmission to humans requires contact with infected animals Infections of humans are usually mild Can result in pox and scars but little other damage Edward Jenner used cowpox to immunize individuals against smallpox Increase in monkeypox cases in humans over the past decade

10. © 2014 Pearson Education, Inc. Herpesviridae Linear dsDNA viruses Have enveloped polyhedral capsids Viral envelope acquired from the host cell's nuclear membrane Viral envelope fuses with the cell membrane to facilitate entry into cell Most prevalent DNA viruses Often latent Remain inactive inside infected cells Reactivation causes recurrence of the disease manifestations Species names combine "HHV" and a number indicating order in which they were discovered

11. © 2014 Pearson Education, Inc. Herpesviridae Infections of Human Herpesvirus 1 and 2 Often result in slow-spreading skin lesions Formerly known as herpes simplex virus or HSV Two species Human herpesvirus 1 (HHV-1) Human herpesvirus 2 (HHV-2)

12. © 2014 Pearson Education, Inc. Herpesviridae Infections of Human Herpesvirus 1 and 2 Types of HHV-1 and HHV-2 infections Oral herpes Genital herpes Ocular herpes Whitlow Neonatal herpes

13. © 2014 Pearson Education, Inc. Figure 24.8 Two manifestations of herpesvirus infections.

14. © 2014 Pearson Education, Inc. Herpesviridae Infections of Human Herpesvirus 1 and 2 Types of HHV-1 and HHV-2 infections Neonatal herpes Babies most often infected during birth Infections can be severe and have a high mortality rate Other herpes simplex infections Herpes gladiatorum can occur in athletes HHV-1 and HHV-2 may also cause encephalitis, meningitis, and pneumonia in immunosuppressed individuals

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16. Herpesviridae Infections of Human Herpesvirus 1 and 2 Epidemiology and pathogenesis of HHV-1 and HHV-2 infections Active lesions are the usual source of infection Asymptomatic carriers shed HHV-2 genitally Transmission occurs through close body contact Enter body through cracks or cuts in mucous membranes Viral replication in epithelial cells leads to lesion formation Virus spreads from cell to cell through syncytia formation HHV-1 infections typically occur via casual contact in children HHV-2 infections occur between ages of 15 and 29 from sexual activity

17. © 2014 Pearson Education, Inc. Herpesviridae Human Herpesvirus 3 (Varicella-Zoster Virus) Infections Causes two diseases Varicella Often called chickenpox Typically occurs in children Herpes zoster Also called shingles Usually occurs in adults

18. © 2014 Pearson Education, Inc. Herpesviridae Human Herpesvirus 3 (Varicella-Zoster Virus) Infections Epidemiology and pathogenesis of HHV-3 (VZV) infections Chickenpox is highly infectious disease Virus enters skin through the respiratory tract or eyes Virus travels via the blood from infection site throughout body Characteristic skin lesions appear 2–3 weeks after infection The disease is usually mild in children Chickenpox in adults is typically more severe Latent virus can reactivate, producing a rash known as shingles Lesions occur along band of skin called a dermatome

19. © 2014 Pearson Education, Inc. Figure 24.9 Characteristic chickenpox lesions.

20. © 2014 Pearson Education, Inc. Figure 24.11 Shingles, the rash caused by Varicellovirus.

21. © 2014 Pearson Education, Inc. Herpesviridae Human Herpesvirus 3 (Varicella-Zoster Virus) Infections Diagnosis, treatment, and prevention of HHV-3 (VZV) infections Diagnosis Chickenpox is diagnosed from the characteristic lesions Shingles lesions can be more difficult to diagnose Treatment Chickenpox is usually self-limiting Shingles treatment involves management of symptoms Prevention Difficult to prevent exposure, since virus is shed before obvious signs appear Vaccines against chickenpox and shingles are available

22. © 2014 Pearson Education, Inc. Herpesviridae Human Herpesvirus 4 (Epstein-Barr Virus) Infections Also referred to as EBV Can cause a number of different diseases

23. © 2014 Pearson Education, Inc. Figure 24.12 Diseases associated with Epstein-Barr virus.

24. © 2014 Pearson Education, Inc. Herpesviridae Human Herpesvirus 4 (Epstein-Barr Virus) Infections Epidemiology and pathogenesis of HHV-4 (EBV) infections Transmission usually occurs via saliva Initially infect epithelium of pharynx and parotid salivary glands Virus enters the bloodstream and invades B lymphocytes Becomes latent and suppresses apoptosis of B cells Immune response causes infectious mononucleosis symptoms Cytotoxic T cells kill virus-infected B lymphocytes Infection in adults produces more serious signs and symptoms Cancer development appears to depend on various cofactors Extreme diseases arise in individuals with T cell deficiency

25. © 2014 Pearson Education, Inc. Herpesviridae Human Herpesvirus 5 (Cytomegalovirus) Infections Infected cells become enlarged One of the more common infections of humans 50% of the adult population in the U.S. is infected 100% of the population of some countries test positive for antibodies against CMV

26. © 2014 Pearson Education, Inc. Herpesviridae Human Herpesvirus 5 (Cytomegalovirus) Infections Epidemiology and pathogenesis of HHV-5 (CMV) infections Transmission occurs through bodily secretions Requires close contact and a large exchange of secretion Usually occurs via sexual intercourse Also transmitted by in utero exposure, vaginal birth, blood transfusions, and organ transplants Most CMV infections are asymptomatic Complications in fetuses, newborns, and immunodeficient patients Newborns may develop signs of infection or mental retardation AIDS patients or immunosuppressed adults may develop pneumonia, blindness, or mononucleosis

27. © 2014 Pearson Education, Inc. “Owl’s eyes” cell Figure 24.13 An owl’s eyes cell.

28. © 2014 Pearson Education, Inc. Herpesviridae Other Herpesvirus Infections Human herpesvirus 6 (HHV-6) In the genus Roseolovirus Causes roseola Characterized by pink rash on face, neck, trunk, and thighs May be linked to multiple sclerosis Can cause mononucleosis-like symptoms HHV-6 may make individuals more susceptible to AIDS Human herpesvirus 8 (HHV-8, Rhadinovirus) Causes Kaposi's sarcoma Cancer often seen in AIDS patients

29. © 2014 Pearson Education, Inc. Figure 24.15 Kaposi’s sarcoma.

30. © 2014 Pearson Education, Inc. Papillomaviridae and Polyomaviridae Double-stranded DNA viruses Have small, naked, icosahedral capsid Once classified as a single family of viruses

31. © 2014 Pearson Education, Inc. Papillomaviridae and Polyomaviridae Papillomavirus Infections Cause papillomas Commonly known as warts Benign growths of the epithelium of skin or mucous membranes Papillomas form on many body surfaces Often painful and unsightly Genital warts associated with an increased risk of cancer

32. © 2014 Pearson Education, Inc. Papillomaviridae and Polyomaviridae Papillomavirus Infections Epidemiology and pathogenesis of papillomavirus infections Transmitted via direct contact and via fomites Autoinoculation spreads from one location to another on a person Warts take three to four months to develop following infection

33. © 2014 Pearson Education, Inc. Papillomaviridae and Polyomaviridae Polyomavirus Infections Capable of causing tumors in animals and humans Can cause other diseases BK and JC viruses are endemic worldwide Infection outcome depends on the individual's immune system Normal immune systems tend to prevent latent infections Compromised immune systems allow latent infections to become established in the kidneys

34. © 2014 Pearson Education, Inc. Papillomaviridae and Polyomaviridae Polyomavirus Infections Reactivation events are different between the BK and JC viruses BK virus Potentially severe urinary tract infections can develop JC virus Can cause progressive multifocal leukoencephalopathy Viruses infect and kill the white matter of the CNS Paralysis and death eventually result Beta interferon can prevent kidney damage by BK virus Diagnosis of JC virus infections often made too late to treat

35. © 2014 Pearson Education, Inc. Adenoviridae Contain single, linear dsDNA genome Have naked polyhedral capsid with spikes One of many causative agents of the common cold Spread via respiratory droplets Can survive on fomites and in improperly chlorinated water Respiratory infections Viruses taken into cells lining the respiratory tract via endocytosis Cause sneezing, sore throat, cough, headache, and malaise Infection of the intestinal tract can produce mild diarrhea Infection of the conjunctiva can result in pinkeye Treat early stages of infection with gamma interferon Attenuated vaccine is available only for military personnel

36. © 2014 Pearson Education, Inc. Figure 24.18 Adenoviral conjunctivitis (pinkeye).

37. © 2014 Pearson Education, Inc. Hepadnaviridae Enveloped DNA viruses Have icosahedral capsids Invade and replicate in liver cells Include hepatitis B virus (HBV) Unique genome is composed of both single- and double-stranded DNA HBV replicates through an RNA intermediary Unique among DNA viruses Reverse transcriptase transcribes DNA genome into RNA

38. © 2014 Pearson Education, Inc. Hepadnaviridae Hepatitis B Infections Cause hepatitis Inflammation of the liver HBV is the only DNA virus that causes hepatitis Viral infection can cause severe liver damage Various symptoms Jaundice, liver enlargement, abdominal distress, and bleeding into the skin and internal organs Co-infection with hepatitis D virus increases risk of permanent liver damage

39. © 2014 Pearson Education, Inc. Figure 24.20 Jaundice.

40. © 2014 Pearson Education, Inc. Hepadnaviridae Hepatitis B Infections Epidemiology and pathogenesis of HBV infections Liver cells continually release virions into the blood Virions are shed into saliva, semen, and vaginal secretions Transmitted when infected body fluids contact breaks in the skin or mucous membranes Virus spread through infected needles, sexual intercourse, and passage to babies during childbirth Many individuals are asymptomatic or have mild symptoms Vaccination has reduced the cases of HBV in the U.S.

41. © 2014 Pearson Education, Inc. Hepadnaviridae Hepatitis B Infections Diagnosis, treatment, and prevention of HBV infections Diagnosis Diagnose by detecting presence of viral antigens Body fluids contain three types of virus particles Treatment No universally effective treatment Prevention Vaccination offers long-term protection against HBV Abstinence and monogamy protect against sexually transmitted infection

42. © 2014 Pearson Education, Inc. Hepadnaviridae The Role of Hepatitis B Virus in Hepatic Cancer Evidence shows HBV associated with hepatic cancer Hepatic cancer occurs in areas with high prevalence of HBV HBV genome integrated into hepatic cancer cells Hepatic cancer cells express HBV antigen Chronic HBV carriers more likely to develop hepatic cancer Hepatic cancer may be the first cancer eliminated by vaccination

43. © 2014 Pearson Education, Inc. Parvoviridae Only human pathogen with a ssDNA genome Have icosahedral capsid Smallest of the DNA viruses Cause a number of diseases in animals B19 virus is the primary parvovirus of humans Causes erythema infectiosum Also called fifth disease Infection results in a reddening of the skin Sunlight aggravates the condition

44. © 2014 Pearson Education, Inc. Figure 24.23 A case of erythema infectiosum (fifth disease).

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