GIANE CARLA BUMAGAT

Betaherpesvirinae(Cytomegalovirus)

Betaherpesvirinae

Virus classificationGroup: GroupI (dsDNA)Order: HerpesviralesFamily: HerpesviridaeSubfamily:

BetaherpesvirinaeGenera:

Cytomegalovirus

MuromegalovirusProboscivirusRoseolovirus

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

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.

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)

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)

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.

Epidemiology

- Acquire by 40-60% of persons by mid-adult life

- >90% Multiple intimate exposure- <5% Whole blood seropositive donors- 80% Kidneys transplant

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

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.

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

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

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

Laboratory Diagnosis

Specimen of choice:- Urine- Saliva- Broncho-alveolar lavage fluid- Biopsy tissue- Blood (EDTA)

PCR Assay

TREATMENT CONTROL

GanciclovirFoscarnent

Screening of organ donors & recipients

Blood donor screening

NO VACCINE

Treatment & Control

Gammaherpesvirinae(Epstein – Barr Virus)

SIDOCON, ERISIA SHOROUK A.BMLS -3A

Epstein – Barr Virus (EBV)

Family: HerpesviridaeSubfamily: Gammaherpesvirinaeds DNA; enveloped; icosahedralFirst isolated from malignant Burkitt’s

lyphoma cell

Epidemiology

Developing countriesEarly adulthoodIncubation period: 1-2mos.MOT:

oral route sexual transmission blood transfusion organ transplantation

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

Infectious Mononucleosis

Symptoms Sore throat with pus Marked fatigue Enlarged spleen &

lymph nodes

Prevention & Treatment Avoiding the saliva of

another person No vaccine acyclovir

Burkitt’s Lymphoma

Children in East Africa and New GuineaCancer starts in B cellsFastest growing human tumorPatients: elevated titers of EBV antibodies

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