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The DNA Viruses

Chapter 24

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General Features of Viruses

• Obligate Intracellular Parasites• Very small (ultramicroscopic)• Non-cellular• Not Alive• Protein Coat (capsid)• Some have envelopes

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Viruses

• obligate intracellular parasites• infect animals, plants, & other microbes, etc.

- all forms of life have viruses that infect them

• All DNA viruses are double-stranded except for parvoviruses, which have ssDNA.

• All RNA viruses are single-stranded except for dsRNA reoviruses.

• Viruses are limited to a particular host or cell type. (Host Range)

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Viruses• Viral infections range from very mild and

self-limiting to life-threatening.

• Many viruses are strictly human in origin, others are zoonoses, some transmitted by vectors.

• Most DNA & a few RNA viruses can become permanent resident of the host cell.

• Several viruses can cross the placenta & cause developmental problems.

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Poxviruses• produce eruptive skin pustules called pocks or pox,

that leave scars• largest & most complex animal viruses• have the largest genome of all viruses• dsDNA….enveloped• examples

– Variola – cause of smallpox– Vaccinia – closely related virus used in vaccines– Monkeypox– Cowpox

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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• vaccine reintroduced in 2002 (bioterrorism threat)

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Smallpox

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Edward Jenner

• COWPOX• People can catch cowpox by direct contact with an infected animal and

they then go on to develop pustules, on their hands.• These are quite painful and there is a general feeling of being unwell.

The incubation period is about 1 week and the illness lasts about 4-6 weeks. There is a full recovery.

• It had always been noticed in rural communities that dairy maids who caught cowpox would never get smallpox- they were immune.

• Jenner rubbed cowpox pus into scratches of a rural farmboy (James Phipps) who then got cowpox. Jenner challenged with smallpox , but the boy did not get smallpox

Statue of Edward Jenner Showing Jenner transferring pus from the hands of someone infected with cowpox into

scratches in skin of a young boy

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Molluscum contagiosum

• caused by an unclassified poxvirus• in endemic areas it is primarily an infection of children• transmitted by direct contact & fomites• in US, most commonly an STD• AIDS patients suffer an atypical form which attacks

the skin of the face & forms tumorlike growths• treatment: freezing, electric cautery, chemical agents

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Herpesviridae• Large, enveloped, icosahedral (20-sided polyhedron), dsDNA• large family of viruses; 8 infect humans

– HSV-1– HSV-2– VZV – CMV– EBV– HHV-6– HHV-7– HHV-8

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Herpesviruses

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Herpesviridae

• latency & recurrent infections

• “Herpes is Forever”

• complications of latency & recurrent infections become more severe with age, cancer chemotherapy, etc

• Among the most common & serious opportunists among AIDS patients

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Herpes Simplex viruses

• HSV-1- lesions on the oropharynx, cold sores, fever blisters– occurs in early childhood

• HSV-2 lesions on the genitalia– can be spread without visible lesions

• humans only reservoir• treatment: acyclovir, famciclovir,

valacyclovir

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Herpes Simplex Virus-1

Latency in trigeminal nerve ganglion

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HSV-1

gingivostomatitis

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HSV-2

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Varicella-Zoster Virus (VZV)

• causes chickenpox & shingles• transmitted by respiratory droplets & contact• primary infection – chickenpox – vesicles• virus enters neurons & remains latent• later, reactivation of the virus results in shingles

with vesicles localized to distinctive areas, dermatomes

• treatment : acyclovir, famciclovir, interferon• live attenuated vaccine

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Chickenpox

Shingles

Early symptoms are acute pain and redness of dermatome followed by rash

VZV Latency and Reactivation

VZV Latency and Reactivation

VZV Latency and Reactivation

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Cytomegalovirus (CMV)• produce giant cells • transmitted in saliva, respiratory

mucus, milk, urine, semen, cervical secretions & feces

• commonly latent in various tissues

• most infections are asymptomatic• Almost all people have been

exposed to CMV by the time they reach adulthood.

• 3 groups develop a more virulent form of disease: fetuses, newborns, immunodeficient adults

Giant cell

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CMV• newborns may exhibit enlarged liver & spleen,

jaundice, capillary bleeding, microcephaly, & ocular inflammation, may be fatal– Babies who survive develop neurological

sequelae; hearing, visual disturbances & mental retardation

• perinatal CMV infection – mostly asymptomatic, or pneumonitis, & a mononucleosis-like syndrome

• AIDS patients – CMV mononucleosis, disseminated CMV, retinitis,

• transplant patients - pneumonitis, hepatitis, myocarditis, meningoencephalitis

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Epstein-Barr Virus (EBV)• infects lymphoid tissue & salivary glands• transmission – direct oral contact & contamination with

saliva• by mid-life 90-95% of all people are infected.• causes mononucleosis – sore throat, high fever,

cervical lymphadenopathy• Because of great sanitation in U.S. 70% of college-age

Americans have never had the infection…so a very vulnerable population for mono

• Long incubation period (30-50 day incubation)• most cases of infection are asymptomatic• Burkitt’s lymphoma associated with chronic

coinfections with malaria, etc

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Infectious mononucleosis (EBV)

Swollen tonsils and gray-white exudate

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Burkitt lymphoma

B-lymphocyte tumor associated with chronic EBV infection

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Diagnosis: leukocytosis with large odd lymphoctes

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Human Herpes Virus 6 (HHV-6)

• Also known as human T-lymphotropic virus• transmitted by close contact with saliva, other secretions• very common –95% prevalent• causes roseola, an acute febrile disease in babies 2-12

months• begins with fever, followed by a faint rash• usually self-limited• adults may get mono-like symptoms, lymphadenopathy,

hepatitis• over 70% of Multiple Sclerosis patients show signs of

infection (Meaning of this linkage???)

• can cause encephalitis, cancer

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Roseola

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• HHV-7 is closely related to HHV-6 causes similar diseases

• Kaposi’s sarcoma-associated virus or HHV-8 is linked with common tumor of AIDS patients, also may be involved in multiple myeloma

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Hepadnaviruses

• enveloped DNA viruses

• never been grown in tissue culture

• unusual genome containing both double & single stranded DNA

• tropism for liver

• Hepatitis B virus causes hepatitis & can be a factor in liver cancer

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Unusual genome

Circular, with part ds DNA and part ss DNA

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Viral hepatitis

• hepatitis – an inflammatory disease of liver cells that may result from several viruses

• interferes with liver’s excretion of bile pigments, bilirubin accumulates in blood & tissues causing jaundice, a yellow tinge in skin & eyes

• caused by 3 principal viruses

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Hepatitis B virus

• multiplies exclusively in the liver, which continuously seeds blood with viruses

• 107 virions/mL blood (a lot)• minute amounts of blood can transmit infection• sexually transmitted• high incidence among homosexuals & drug addicts• can become a chronic infection• increases risk of liver cancer• chronic infection controlled with interferon• HBV vaccine –given in 3 doses over 18 months

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HBV (clinical features)

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Adenoviruses

• nonenveloped, ds DNA• 30 types associated with human disease• infect lymphoid tissue, respiratory & intestinal epithelia

& conjunctiva• oncogenic in animals, not in humans• spread by respiratory & ocular secretions• causes colds, pharyngitis, conjunctivitis,

keratoconjunctivitis, acute hemorrhagic cystitis– Adenovirus is only one of many viruses that can cause “the

common cold”!

• vaccine available

Adenoviral pinkeye

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PapovavirusesThis term/grouping of viruses is becoming less often used

• Papillomavirus

• Polyomavirus

• Simian vacuolating virus

• small nonenveloped icosahedra (20-sided polyhedron) with dsDNA

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Papillomavirus

• papilloma – benign, squamous epithelial growth, wart or verruca

• caused by 40 different strains of HPV• Common warts (seed warts) – on fingers, etc• plantar warts – on soles of feet• genital warts – prevalent STD• transmissible through direct contact or

contaminated fomites, autoinnoculation (self-spread)

• Incubation – 2 weeks – more than a year

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Papillomavirus

Common wart

Plantar wart

Genital wart

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Genital warts

• most common STD in US• over 6 M new cases each year• 30 M carriers of one of the 5 types of HPV

associated with genital warts• CDC estimates sexually active people have a 50%

chance of catching HPV during a lifetime• strong association with cervical & penile cancer • Vaccine available

HPV Vaccine

• For girls and women 9-26 years of age

• Three doses– Initial– 2 month booster– 6 month booster

• For prevention only…not a treatment

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Polyomaviruses

• induce tumors • JC & BK viruses (named after patients from which the viruses were

first isolated)

• common throughout the world• majority of infections are asymptomatic or mild• not much is known• BK infection in renal transplants causes

complications in urinary function• Progressive multifocal leukoencephalopathy

(PML) is an uncommon fatal infection by JC

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Parvoviruses• nonenveloped icosahedral virus, ssDNA• very small diameter & genome size• causes distemper in cats, enteric disease in dogs,

fatal cardiac infection in puppies

• B19 variety causes fifth disease, (erythema infectiosum), rash of childhood– Child may have fever & rash on cheeks– Severe fatal anemia can result if pregnant woman

transmits virus to fetus

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Parvoviruses

“slapped face” rash of fifth disease.