Pox viruses and other DNA families

poxviridae family : dr. jawad k. al-khafaji

poxviruses have three medical important viruses: smallpox, cowpox and monkeypox.
smallpox virus (a.k.a variola virus):
variola virus is highly contagious and transmitted from person to person by respiratory dropinglets or by direct contact with infected patients. no animal reservoir or vector. no latency in man.
the virus cause a severe disease in man but which has now been eliminated by intensive international vaccination . the virus was eradicated from all parts of the world in 1977 by global use of vaccine. the success of eradication is dependent upon critical factors
(i) smallpox virus is largest , and has single, stable serotype.
(ii) effective vaccine is available.
(iii) the disease is easily recognized clinically.
(iv) the antibody is prompt, therefore, exposed persons can be protected .
(v) there is no animal reservoir, and human is only host.
(vi) there is no carrier state or subclinical infection.
pathogenesis:
the virus is acquired by inhalation of contaminated air dropinglets, and infects epithelial cells of upper respiratory tract , or acquired by invasion of broken skin. the virus multiplies in regional lymph nodes (the virus replicates in cytoplasm) and spreads via the blood stream to spleen and liver. the virus is disseminated by a secondary viremia to the skin , where lesions develop. recovery from the disease confers lifelong immunity.
clinical manifestations:
smallpox has an incubation period of 10-14 days 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 . the rash evolves through stages from macules to papules , vesicles, pustules ,and finally , crusts in 2-3 weeks.
rather similar to severe chicken pox (varicella). abrupt onset of fever and prostration with a macular rash on the third day (head, limbs, hands and feet rather than trunk, including palms and soles). progressed to vesicles which become pustular, ulcerated, scabbed, healed with scarring ("pock marked face"). 16 to 30% mortality.

lab. dx:
1-direct diagnosis of virus by electron microscope .
2-isolation of virus by growing in cell culture or in chick embryo .
3-detection of viral antigens in vesicular fluid by immunofluorescence test.
4-dna of the virus can be detected by pcr.
control :
a.treatment:
cidofovir is used for therapy of variola infections.
b.prevention:
attenuated vaccine is available ,which made from related viruses ,cowpox virus (a.k.a vaccinia virus).


non-enveloped dna viruses:

adenoviridae family :

adenoviruses : they have about 50 different human serotypes and 100 serotypes in animals and birds. adenoviruses were originally isolated from adenoids , from which the name is derived.
adenoviruses are transmitted by variety modes by respiratory route , by fecal-oral route ,or through direct inoculation of eyes by fingers(ocular secretions). adenovirus infections are endemic worldwide and are more prevalent in young children. outbreak occur in military recruits because of close living conditions that facilitate transmission.
pathogenesis:
adenoviruses infect epithelial cells of respiratory tract and intestinal tract and cause direct cytotoxic damage. the virus may spread to involve lymphoid tissues and can persist as a latent infection in tonsils and adenoids.
clinical findings:
adenovirus types 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 ,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.



lab. dx:
1-adenovirus infection can be diagnosed by virus isolation and detection in cell culture.
2-serology tests such as cft.
3- antigenic detection by pcr.
control:
a. treatment: there is no specific antiviral therapy for adenoviruses.
b. prevention:
1. there are no vaccine available for civilian use , but some vaccines are used only in military.
2. handwashing and good infection-control practices are effective in preventing adenovirus infections.


parvoviridae family :

parvovirus b19(now called erythrovirus): is very small ,non-enveloped virus with ssdna. the capsid has icosahedral symmetry. there is 4 serotypes.
human are natural reservoir animals are not source of human infections. b19 virus 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 (erythroblsts) in the bone marrow ( which accounts for aplastic anemia),and endothelial cells in blood vessels( which accounts for erythema infectiosum) .
b19 infects erythroid precursors and replicate in them ,resulting in suppression of erythropoiesis , and cause anemia .the virus replicates(in nucleus) only in s-shape of immature cells ,which explain why the virus replicates in rbc precursors but not in mature red cells .
immune complexes composed of virus and igm or igg also contribute to pathogenesis of rash and to arthritis . infection provides lifelong immunity against re-infection.
clinical manifestations:
b19 causes erythema infectiosum 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 ("slapped-cheeks" appearance) followed by a rash on the trunk and limbs. the rash initially has a discrete erythematous maculopapular appearance and then becomes reticular, disappearing in 1 to 3 weeks. erythema infectiosum often resembles the rash of rubella(measles). outbreaks occur predominantly in spring, mainly in school children and young adults.
b19 infections of children with chronic anemia (such as sickle cell anemia, thalassemia) can have severe aplastic anemia .
infection of adults , especially women , can cause arthritis mainly in small joints of hands and feet bilaterally.
the virus may transmitted cross placenta from infected mother and infect the her fetus . the infection during first and second trimester 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.
lab.dx:
a-b19 virus infection is diagnosed by detection of b19-specific igm.
b-molecular technique such as : pcr detection of viral dna.
control:
a. treatment: there is no specific antiviral therapy for b19 virus.
b. prevention: there is no vaccine to prevent b19 virus infections.


papovaviridae family:
the term "papovavirus" was derived from the first two letters of the names of three members of this group: papillomavirus, mouse polyoma virus, and simian vacuolating virus (sv40). they are inducing tumor in their natural hosts.
human papillomaviruses (hpv): are small, nonenveloped , dsdna and that replicate in the nucleus. hpvs have more than 120 genotypes.
hpvs are transmitted by direct contact with infected individuals, sexual contact or transmitted indirectly by contact with fomites .
papillomaviruses are widely distributed. the viruses occur in many animals (including rabbits, cows, and dogs) as well as man. human papillomaviruses do not infect any animal hosts.
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 remain 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.


clinical findings:
hpv types 1,2, and 4 cause papillomas that often called 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 . cofactors are most probably involved in the progression of high-risk human papillomavirus lesions to carcinomas. suspected cofactors include irradiation, carcinogenic products of tobacco smoke, and genital infection by herpes simplex virus.
lab. dx:
1-hpv can not be isolated in cell culture. no serological tests are available.
2-hpv infections are usually diagnosed clinically.
3-cytological smear is gold standard in diagnosis of cervical cancer.
4-detection of the virus is based on molecular techniques using pcr.
control :
a. treatment:
(i) the warts are treated surgically.
(ii)cidofovir and interferon are used for treatment of warts. the trichloroacetic acid can be used as topical agent.
b. prevention: no vaccine is available for hpv, but now hpv vaccine is in development.