DNA viruses: Smallpox and other DNA viruses

college of medicine microbiology
medical virology
dna viruses (continued): dr. jawad kadhim tarrad

smallpox(variola) virus :
• genus: orthopoxvirus.
• it has one serotype.
important properties:
• it is member of family poxviridae.
• it is largest virus and brick shape.
• it has complex symmetry.
• it has dsdna
• enveloped virus.
source and transmission:
• natural host is human. no animal reservoir or vector.
• it is transmitted from person to person by
1. respiratory dropinglets or by
2. direct contact with infected patients.
pathogenesis:
• the virus infects epithelial cells of upper respiratory tract , or acquired by invasion of broken skin. the virus multiplies in lymphoid tissues (regional lymph nodes) , the virus replicates in cytoplasm, and spreads via the blood stream to spleen and liver.
• the new viruses are disseminated by a secondary viremia to the skin, where lesions develop.
diseases and clinical features:
• after i.p: 10-14 days, the virus cause severe disease, smallpox disease with abrupt onset of fever, chills, headache, backache, and myalgia , followed by rash 3-4 days later.
• the rash is distributed on face and trunk(head, limbs, hands and feet rather than trunk, including palms and soles). the rash progressed through stages from macules to papules , vesicles, pustules ,and finally , crusts in 2-3 weeks healed with scarring.
• in severe case, the rash was hemorrhagic with fatality rate varied from 5-40%. in mild variola(called variolla minor), or in vaccinated persons, the mortality rate was under 1%.
• recovery from the disease confers lifelong immunity. the attack of smallpox gave complete protection against reinfection.
epidemiology:
• variola virus is highly contagious.
• the disease in man has now been eliminated in all parts of world by intensive international vaccination in 1980 .
• the success of eradication is dependent upon critical factors:
1. smallpox virus is largest, and has single and stable serotype.
2. effective vaccine is available.
3. the disease is easily recognized clinically.
4. the exposed persons can be protected by antibodies.
5. there is no animal reservoir, and human is only host.
6. there is no carrier state or sub-clinical infection.
lab. dx:
• isolation of virus by growing in cell culture or in chick embryo .
• detection of viral antigens in vesicular fluid by immunofluorescence test.
• dna of the virus can be detected by pcr.
control :
• treatment: cidofovir is used for therapy of variola infections.
• prevention: attenuated vaccine is available, which made from cowpox virus (a.k.a: vaccinia virus) by edward jenner in 1796(first vaccine). vaccination induced immunity against virus for 5 year or more. jenner observed that those who have had cowpox are immune to smallpox.
others poxviruses such as: cowpox, monkeypox, buffalopox are cause human infections in rarely.
mulluscum contagiosum cause many benign skin nodules (wart-like tumors) on face, arms, back and buttocks.
adenovirus :
• genus: mastadenovirus.
• it has 50 or more different human serotypes and 100 serotypes in animals and birds.
• human adenoviruses are divided into 6 groups(a-f).
important properties:
• it belongs to adenoviridae family
• it has dsdna.
• nucleocapsid has icosahedral.
• non-enveloped virus.
source and transmission:
• humans are natural host.
• adenoviruses are transmitted by variety modes:
1. respiratory route(in respiratory tract).
2. fecal-oral route (in git) .
3. direct inoculation (ocular secretions)of eyes by fingers.
pathogenesis:
• adenoviruses infect epithelial cells of respiratory tract , intestinal tract and eye , and cause direct cytotoxic damage. the virus attaches to epithelia via fiber structures of virus and then adsorbed by endocytosis. adenovirus replicates in nucleus of infected cells.
• the virus may spread to involve lymphoid tissues and can persist as a latent infection in tonsils and adenoids. the latent state can be reactivation by immunosupression.
diseases and clinical findings:
• incubation period is usually 1-2 weeks.
• adenovirus serotypes 1-7 cause urt illness such as common cold, pharyngitis, and tonsillitis in infants and young children, which are characterized coryza, fever, cough, and lymphadenopathy. 20% of children have lrt infection such as pneumonia, which is characterized by bronchitis and bronchiolitis.
• certain adenoviruses are associated with eye infections such as keratoconjunctivitis caused by types 8 ,19 and 37.
• adenovirus types 40 and 41 are second to rotaviruses as cause of acute gastroenteritis in infants and young children.
• adenovirus types 11 and 21 cause hemorrhagic cystitis, which is characterized by fever and hematuria.
• approximately half of all adenovirus infections are asymptomatic. most infections resolve spontaneously.
epidemiology:
• adenovirus exist in all parts of world, the infections are endemic worldwide .
• patients of all ages are affected. most cases prevalent in young children.
• outbreak occurs in human population living in closed condition such as military recruits.
lab. dx:
• isolation and detection in cell culture.
• serology tests such as cft.
• genetic detection by pcr.
control:
• treatment: there is no specific antiviral therapy.
• prevention:
1. there are no vaccine available for civilian use , but some live vaccines are used only in military.
2. hand washing and good infection-control practices are effective in preventing adenovirus infections.
parvovirus b19:
• genus: erythrovirus.
• there are 4 serotypes.
important properties:
• it belongs to parvoviridae family.
• it is very small .
• non-enveloped virus.
• it has ssdna.
• the capsid has icosahedral symmetry.
source and transmission:
• human are natural reservoir animals are not source of human infections.
• parvovirus b19 is can be transmitted from person to another by respiratory route, and blood donated for transfusions, also transplacentally from infected mother to fetus.
pathogenesis :
• the virus infects two types of cells rbcs precursors (erythroblasts) in the bone marrow ( which accounts for aplastic anemia),and endothelial cells in blood vessels( which accounts for erythema infectiosum) .
• b19 virus infects erythroid precursors and replicate in them, resulting in suppression of erythropoiesis , and cause anemia . the virus replicates only in s-shape of immature cells ,which explain why the virus replicates in rbc precursors but not in mature red cells. the virus replicates in nucleus(replication in nucleus result in cell death).
• immune complexes composed of virus and igm or igg also contribute to pathogenesis of rash and to arthritis.
diseases and clinical findings:
• parvovirus b19 causes erythema infectiosum(fifth disease) in children which characterized by bright red rash on face, giving slapping-cheek appearance, with low fever ,coryza (runny nose) and sore throat . the rash develop in 17-18 days after acquire the virus . the first sign of illness is marked erythema of the cheeks followed by a rash on the trunk and limbs. erythema infectiosum often resembles the rash of rubella(measles).
• b19 virus infections of children with chronic anemia (such as sickle cell anemia, thalassemia) can have severe aplastic anemia .
• the virus may transmitted cross placenta from infected mother and infects her fetus. the infection during first and second trimester of pregnancy can lead to fetal anemia ,congestive heart failure and death which called hydropings fetalis , whereas infection during third trimester do not result in important clinical findings.
• infection of adults , especially women , it can be cause arthritis mainly in small joints of hands and feet bilaterally.
epidemiology:
• most cases occur in children and young adults.
• outbreak occurs in spring months.
• infections are most commonly seen as outbreak in school.
• infection provides lifelong immunity against re-infection.
lab.dx:
• detection of antibodies against virus , b19-specific igm.
• pcr detection of viral dna.
control:
• treatment: there is no specific antiviral therapy. aplastic anemia may require blood transfusion therapy.
• prevention: there is no vaccine. good hygienic practices should help prevent the infection.
human papillomavirus (hpv):
• genus: papillomavirus.
• it has more than 120 genotypes.
important properties:
• it belongs to papovaviridae family
• small virus and spherical shape.
• non-enveloped virus .
• it has dsdna.
• it has icosahedral nucleocapsid.
transmission:
• human and animals are natural hosts.
• hpvs are transmitted by
1. direct contact with infected individuals.
2. sexual contact.
3. contact with fomites .
pathogenesis:
• papillomaviruses have a high tropism for epithelial cells of the skin and mucous membranes. hpv virus targets squamous epithelial cells and gains entry through cracks(abrasions) in the skin or tears or lacerations in mucosal surfaces during sexual intercourse .
• the infection either remain localized and may resolve spontaneously, or it remains as latent, may be progress to dysplasia and carcinoma.
• the viruses have carcinogenic genes, hpv encodes some proteins that inactivate tumor suppressor proteins in human cell , and stimulate cell proliferation which become cancer cell.
diseases and clinical findings:
• hpv types 1,2, and 4 cause papillomas that often called skin warts ( benign tumor) on the hands and feet.
• hpv types 6 and 11 cause genital warts(condyloma acuminate) also cause laryngeal papillomas in children infected during birth canal of mother with genital warts.
• hpv types 16 and 18 are associated with carcinoma (may be become malignant tumor) of uterine, cervix ,penis and anus .
epidemiology:
• papillomaviruses are widely distributed.
• estimated 660 million people worldwide have hpv genital infection. over 90% of cervical cancer cases and over 80% of anal cancer cases are linked to genital infection with hpv.
• the viruses infect many animals (including rabbits, cows, and dogs) as well as man.
• human papillomaviruses do not infect any animal hosts.
• cofactors associated with carcinomas include irradiation, carcinogenic products of tobacco smoke, and genital infection by hsv-2.
lab. dx:
• hpv can not be isolated in cell culture.
• no serological tests are available.
• cytological smear is gold standard in diagnosis of cervical cancer.
• detection of the virus by using pcr.
control :
• treatment:
1. warts are treated surgically.
2. cidofovir and interferon are used for treatment of warts.
3. trichloroacetic acid can be used as topical agent.
• prevention: attenuated hpv vaccines are available, but these vaccines are not recommended for pregnant females.