beta & gamma herpesvirinae
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GIANE CARLA BUMAGAT
Betaherpesvirinae(Cytomegalovirus)
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Betaherpesvirinae
Virus classificationGroup: GroupI (dsDNA)Order: HerpesviralesFamily: HerpesviridaeSubfamily:
BetaherpesvirinaeGenera:
Cytomegalovirus
MuromegalovirusProboscivirusRoseolovirus
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STRUCTURE GENOME
o Enveloped o Spherical to Pleomorphico 150-200 nm in diameter,o Icosahedral symmetryo Capsid consists of 162
capsomers and is surrounded by an amorphous tegument.
o Glycoproteins complexes are embeded in the lipid envelope.
o Monopartiteo Linearo dsDNA genome of 140-
240 kb. (The genome contains terminal and internal reiterated sequences.)
Betaherpesvirinae
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Cytomegalovirus (CMV)
- From the Greek cyto-"cell" & megalo-"large“
- Human cytomegalovirus alternatively known as Human herpesvirus 5 (HHV-5)
- Largest genetic content of Herpesvirus.
- “Oldest” type of herpesvirus in evolutionary terms.
- Very specific species & Cell-type specific.
- CMV is detected in histopathological sections by visualization of owl's eye inclusion bodies.
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SPECIES
o Type: - Human cytomegalovirus (HHV5)
o Main:- Cercopithecine herpesvirus 5 (CeHV-5) - Cercopithecine herpesvirus 8 (CeHV-8) - Pongine herpesvirus 4
(PoHV-4)
Cytomegalovirus (CMV)
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CELL TROPISM HHV-5
- Mucosal epithelium of the genitourinary tract
- Upper alimentary tract, or respiratory tract is the primary site of infection.
- Followed by a leukocyte-associated viremia
- Wide range of infected tissues Latency: remains latent in lineage-committed myeloid cells
IN VITRO:- Human fibroblast cells
are required for isolation of the virus in vitro.
IN VIVO:- Salivary Glands- Kidneys- Respiratory tract- Other epithelial
(endothelial) sites
Cytomegalovirus (CMV)
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Transmission
- Humans are the only reservoir for human CMV and transmission occurs by person to person contact.
- CMV is very labile and close or intimate contact is necessary for spread of infection
- Sources of infection include oropharyngeal secretions, urine, cervical and vaginal secretions, breast milk, tears, feces and blood.
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Epidemiology
- Acquire by 40-60% of persons by mid-adult life
- >90% Multiple intimate exposure- <5% Whole blood seropositive donors- 80% Kidneys transplant
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INFECTION
Virus shed in:- Body secretion- Urine- Semen- Breast milk- Cervical fluid
Mononuclear cells carry the latent virus genome & viral RNA transcript.
Bone Marrow- Prime sit of the latency
Macrophage can enter the replication cycle.
Reactivation- EndogenousRe-infection- ExogenousEndothelial cells
(Multinucleate cells) found in the circulation during disseminate CMV infection. These cells are fully permissive for CMV replication
Pathogenesis
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Intra-uterine infection
Maternal viraemia may result fetal infection.
Acquired in utero when mother suffers in CMV reactivation (rare).
Transplacental infection carried by infected cells & transmission associated with a high viraemic load.
Cause damage to target cells.
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Perinatal infection Postnatal infection
Acquired from infected maternal genital tract secretion or breast-feeding.
Acquired by:- Saliva- Semen- Whole blood
transfusion- Organ transplant
All CMV IgG antibody positive cells (“Seropositive”)
Perinatal & Postnatal Infection
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CONGENITAL CMV INFECTION
MONONUCLEOSIS
o Asymptomatic at birtho May show sensorineural
deafness or intellectural impairment.
o Cyromegalic inclusion disease:- Intrauterine growth retardation- Hepatosplenomegaly- Jaundice- Thrombocytopenia- CNS-CMV:
- Microcephaly - Encephalitis- Choriorentinitis
- Myocarditis- Peunomonitis
o Respiratory tract infect is common in infancy.
o Mononucleosis syndrome- reminiscent of symptomatic primary EBV infection.
o Hepatitiso Fevero Atypical lymphocytosis
Clinical features CMV
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IMMUNOCOMPROMISED PATIENT
o Dissemination of the virus in blood indicate: Hectic fever & bad prognostic sign
o Cellular immunodeficiency:- Pneumonitis- Encephalitis- Retinitis- Oseophagitis/ Colitis- Pancreatitis/ Adrenalitis
o AIDS:- Retinitis
o Transplant recipient: Direct- caused by virus Indirect- cause by
interaction w/ immune system
o Transplant protocol: - Prophylaxis- Pre-emptive treatment
Clinical features CMV
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Laboratory Diagnosis
Specimen of choice:- Urine- Saliva- Broncho-alveolar lavage fluid- Biopsy tissue- Blood (EDTA)
PCR Assay
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TREATMENT CONTROL
GanciclovirFoscarnent
Screening of organ donors & recipients
Blood donor screening
NO VACCINE
Treatment & Control
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Gammaherpesvirinae(Epstein – Barr Virus)
SIDOCON, ERISIA SHOROUK A.BMLS -3A
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Epstein – Barr Virus (EBV)
Family: HerpesviridaeSubfamily: Gammaherpesvirinaeds DNA; enveloped; icosahedralFirst isolated from malignant Burkitt’s
lyphoma cell
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Epidemiology
Developing countriesEarly adulthoodIncubation period: 1-2mos.MOT:
oral route sexual transmission blood transfusion organ transplantation
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Infectious Mononucleosis
Kissing disease15-24 years of ageDiagnosis: hematology and serological testAccompanied by the production of heterophile
agglutinins that can be detected by a rapid slide agglutination test (Paul Bunnell test).
Differential WBC count: >50% atypical lymphocytesPresence of heterophile antibodies-Ha testMonospot test Culture from saliva or throat washingsPCR
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Infectious Mononucleosis
Symptoms Sore throat with pus Marked fatigue Enlarged spleen &
lymph nodes
Prevention & Treatment Avoiding the saliva of
another person No vaccine acyclovir
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Burkitt’s Lymphoma
Children in East Africa and New GuineaCancer starts in B cellsFastest growing human tumorPatients: elevated titers of EBV antibodies
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TREATMENT CONTROL
Adoptive humoral immunotherapy EFFECTIVE AGAINST
EBV-ASSTD B CELL TUMORS(PTLD)
Adoptive cellular immunotherapy Effective to individuals
does not respond to any Tx for PTLD
Subunit vaccinesScreening for IgA
Ab to EBV VCA
EBV