Viral exanthems: Lecture 36
Parvoviridae |
SsDNA, dual polarity. Terminal repeats at 3'. codes for 3 proteins. Icosahedral symmetry. Ether resistant, 18-26nm particle. |
B19 |
Autonomous parvoviridae. Primary human cells. Fetal liver and hematopoitic progenitor cells. Requires actively growing cell. Infects immature erythrocytes w/o problems except w/ sickle cell and thalessemia. Persistent anemia in AIDS patients. Erythema infectiosum 5th disease. Incubation 4-12 days. Fever, malaise, headache, itching, confluent and indurated rash on face (slapped cheek) spreads to legs and arms in 1-2 days (lace-like). Lymphadenopathy and splenomegaly in acute cases. Active transplacental transmission. Spreads via respiratory system during spring months in children and young adults. Acute plasticity |
AAV |
Dependovirus. Parvoviridae |
B19 recurrence |
Heat, stress, sunlight, exercise |
Alphaherpesvirinae |
Short, cytolytic replication cycle. Latency in neurons, HHV 1, 2, 3 |
HHV-1 Primary infection |
Mocusa or broken skin to initiate infection. Normally restricted to the oropharynx. Spread by respiratory droplets or saliva. Replication at site of infection. Invades local nerve nedings, transported to the dorsal root ganglia and establish latency. Immunocompromised: viremia, infected organs. |
HHV-1 latent infections |
DNA in trigeminal ganglia in a non-replicating state for the rest of the life. No virus can be recovered between recurrences at or near the usual site of lesions. Only a few immediate early viral genes may be expressed |
Alpha viral genes |
Immediate early genes. |
HHV-1 recurrent infection |
Provocation reactivates the virus. Molecular basis not known. Infectious virion synthesized, follows axons back to peripheral site. Humoral and cellular immunity does not effect this stage. When asymptomatic virions shed in secretion |
Gingivostomatitis |
HHV-1. Children age 1-5. incubation 3-5 days. Course 2-3 weeks. Fever, soar throat, vesicular and ulcerative lesions, edema, gingivostomatitis, submandibular lymphadenopathy and malaise. Adults get pharyngitis and tonsillitis |
Eczema herpeticum |
Intact skin resistant to HHV-1 and HHV-2. Cutaneous infections are severe in patients with skin disorders or burns. Infection of multiple site on skin causing loss of epithelium resulting in loss of body fluids and frequent secondary infections. |
Herpes labialis |
HHV-1 (2). Fever blisters. Recurrent infection, localized to lips. Fades over 4-5 days. Lesions progress through pustular and crusting. No scars. Healing in 8-10 days. Lesions may recur repeatedly at various intervals. Most common infection. |
HHV-2 primary infection |
Genital herpes. Usually vesicular eruption on the genitalia. Spreads by sexual contacts. Affects both sexes. May be associated w/ cervical carcinoma. Often associated w/ herpes labialis |
HHV-2 latent infection |
Viral cells reside in sensory cells of sacral ganglia. No virion or virus structural protein produced |
CMV congenital infctions |
20% symptomatic: jaundice, microencephly, hepatosplenomegaly, and lethargy. Asymptomatic infants develop viruria. |
Perinatal CMV |
Vast majority asymptomatic. Pneumonitis may be seen occasionally during the first 3 months |
CMV in immunocompromised |
Primary &/| reactivation within 2 months of transplantation. Leukemia and lymphoma patients at highest risk. CMV retinitis, colitis, and pneumonia in AIDS |
CMV diagnosis |
Cytomegalic cells. Virus isolation from saliva and urine. EM observation of virus in urine. RIA and ELISA |
Gancyclovir |
CMV treatment. Acyclic guanosine analogue, decreases virus shedding in all patients |
Acyclovir |
CMV is resistant. No viral thymidine kinase |
Human leukocyte interferon |
Delays virus shedding |
Gammaherpesvirinae |
Replication cycle variable length. Lymphoproliferative cytopathology. Latency in lymphoid tissue |
Epstein Barr virus primary infection |
HHV-4. Worldwide distribution in young adults. Unrecognized in children. Non-specific febrile illness, URT: pharygotonsilitis, rash, lymphadenopathy and pneumonia. Adolescent infections and more common. Oral transmission, virus shedding in saliva, virus replicates in parotid glands and gain entrance into blood by infecting B-cells. Dissemination via lymphoreticular system |
EBV latent infection |
Blood, lymphoid tissue, throat. Activation mechanism unknown |
Infectious mononucleosis |
Common in young adults and rare in children. Chills, sweat, malaise, sore throat, fever, and lymphadenopathy. 50% of patients have tonsillopharyngitis w/ thick exudate. 10-15% have hepatomegaly. Ampicillin is given during the infection, 90% of the patients will develop pruritic maculopapular eruptions. Immunocompromised patients: EBV associated lymphomas, functional T-cell defect and NK cell deficiency |
EBV and cancer |
Burkett's lymphoma and nasopharyngeal carcinoma. High incidence in central Africa and China. EBV genome present in over 90% of biopsies. Higher titers against EBV capsid and early antigen (EB Nuclear antigen (EBNA)) |
EBV diagnosis |
Enlarged lymphocytes in peripheral blood (downy cells). Detection of viral DNA in biopsy material. EBV capsid or EBNA detection in cells. Serology: salivary IgA and NPC. Wing scapula (paralysis of serratus anterior). Burkett?? |
EBV treatment |
Self limiting. Requires supportive measures. No contact sports. |
Acyclovir |
Inhibits EBV in vitro |
Vidarabine |
Inhibits EBV in vitro |
HHV-6A |
Grows in T-cells. Latency in resting cells. Mitogenic stimulation causes lytic infection. |
HHV-6B |
Typically occurs in early infancy w/ high fever and rash. Consequences of primary, |
Roseola infantum |
Exanthem sabitum, sixth disease. Characterized by high fever and rash. Involved in lymphadenopathy and hepatitis, mode of transmission unknown. Isolated from saliva and kidneys of patients |
HHV-7 |
Isolated from CD4 T-cells of healthy individuals. Similar to HHV-6. Children under the age of 2 years infected. 97% of adults are serologically positive. Clinical relevance unknown |
HHV-8 |
Isolated from AIDS related Kaposi's sarcoma and body cavity based lymphomas in AIDS patients. Relationship to healthy individuals unclear |
Papovaviridae |
dsDNA. Supercoiled circular. Capsid symmetry: icosahedral. Naked virus. Ether resistant. 45-55nm. Can cause cancer. Chronic infections. Papilloma virus, polyoma virus (JC and BK viruses) |
HPV |
All members cause benign tumors. Free episome associated w/ benign tumors. Random integration or part of the genome essential for malignancy. Flat warts, life long disease, may become malignant due to exposure to sunlight. |
Anogenital warts |
Condylomatous warts. HPV-6 and 11. STD. Malignant transformation in both sexes. Almost all cervical biopsies positive for HPV-6 and 11 antigens or DNA. HPV detected in semen |
HPV diagnosis |
Pap smear: Perinuclear vacuolization and nuclear enlargement; Koilocytosis in cervical epithelium. Detection of viral antigens by immunoassay. PCR. DO NOT GROW IN ROUTINE CELL CULTURE |
Papilloma virus treatment |
Removal of infected epithelium. Systemic and local interferon therapy. Disease recurs when therapy discontinued |
HHV 3 |
Chicken Pox!
|
Poxviridae |
dsDNA. Linear cross linked termini. Capsid symmetry is complex. Enveloped (coat) & ether resistant. Produces skin lesions. Replicates in cytoplasm. Resistant to inactivation by various agens. All enzymes necessary for replication are virus associated or virion coded. Virus coat is NOT acquired by budding and is NOT necessary. Recombinant vaccinia virus good for delivery of immunogens |
Guarnieri bodies |
Eosinophilic cytoplasmic inclusion bodies |
Variola major |
Smallpox |
Vaccinia |
Mild disease, encephalitis. Virus has several antigens similar to variola, but distinct from cowpox. Used as vaccination against variaola. Vaccine produces lasting immunity. Virus replicates in humans. No asymptomatic or undiagnosed cases. Recombinant virus being developed to deliver many immunogens for vaccination. Complications: generalized vaccinia, encephalitis and death. |
Monkeypox |
Found in central Africa. Clinically indistinguishable from smallpox. Human infections recognized following eradication of smallpox. To considered in populations w/ close relationships w/ monkeys. |
Molluscum contagiosum |
STD. Mainly children and young adults. Chronic proliferative process on face, back, legs, buttocks, anus, and genitals. Can be confused w/ herpes. Diagnosis by guarnieri bodies and EM. Vesicles have central depression. |
ORF |
Contagious pustular dermatitis. Sheep disease emerging in humans. Self-limiting vesicles on fingers. NO CYTOPLASMIC INCLUSION bodies. Virion is ovoid in shape. Diagnosis: EM |
Tanapox |
Mild disease mainly around Tana river in Kenya, East Africa. Few pock like lesions on the upper part of the body. Initially resembles smallpox. Pustulation never occurs. Diagnosis by EM. Vesicles have central depression. |
Smallpox |
Variola major and minor. Can not distinguish the 2 viruses. Upper respiratory mucosa, lyphoid tissue, viremia, generalized skin rash. Rash goes from face and hands to trunk and legs. Macule --> papule --> vesicle --> pustule --> scab. All lesions at SAME STAGE. Vesicles have central depression. |
Pox diagnosis |
Generally on symptomology and clinical picture. Cytoplasmic inclusion bodies in infected skin and mucosal cells. Virus isolation from: vesicles, pustules, scabs, blood, and saliva. |
Pox treatment |
Isatin-beta-thisemicarbazone (IBT) and N-methyl IBT (marburan). Inhibit late mRNA synthesis so no capsids are made. Rifampin inhibts some events in viral morphogenesis. Immature virus emerges w/o surface spicules due to mutations in 62K protein. |
Rubeola V. Rubella
Rubeola |
Rubella |
Paramyxoviridae |
Togaviridae |
Morbiliivirus |
Rubivirus |
ss – RNA |
ss + RNA |
Enveloped |
Enveloped |
HA and FA spike |
HA spike |
1 serotype |
1 serotype |
Replicates in cytoplasm |
Replicates in cytoplasm |
Measles |
German measles |
Respiratory droplets |
Respiratory droplets |
Exanthems |
Exanthems |
Febrile disease |
Febrile disease |
High fever/cough |
Mild fever/malaise |
Maculopapular rash |
Maculopapular rash |
Koplik's spots |
Auricular lymphadenopathy |
Conjunctivitis |
Conjunctivitis |
Coryza |
Coryza |
Cough |
Polyarthritis |
Serious complications |
|
Bronchopneumonia, otitis media, encephalitis, giant cell pneumonia, bacterial pneumonia, subacute scelerosing panencephalitis |
Congenital rubella: cataracts and deafness, mental retardation, heart defects; stillbirths |
Diagnosis |
|
Clinical symptoms |
Clinical symptoms |
Multinucleated giant cells |
Kidney cell culture |
Serological diagnosis |
IgM in acute phase serum |
Syncytia in tissue |
Interference assay |
Prevention and treatment |
|
MMR attenuated vaccine |
MMR attenuated vaccine |
Measles immune globulin |
Jeryl Lynn strain |
30,000 cases annually |
~1,500 cases. 50 cases of Rubella syndrome |