Specific Viral Families: Herpesviridae


Herpesviridae


http://pathmicro.med.sc.edu/virol/herpes_simplex.jpg

Above: TEM of Herpes Simplex Virus

Herpesviruses are a leading cause of human viral disease, second only to influenza and cold viruses. They are relatively large, enveloped viruses with linear dsDNA. Herpesviruses are widely distributed in nature.

Important properties

    · Concentric virion with

o Inner core

o Icosahedral capsid

o Amorphous tegument

o Envelope ( glycoprotein)

    · Linear dsDNA

    · Three origin of replication (ORI)

http://pathmicro.med.sc.edu/mhunt/dna15.jpg

Source:

The herpesviruses are known for their ability to cause latent infections.

    · In cells infected with herpesviruses, the viral dsDNA can exist as a provirus.

    · Herpesviruses remain in host cells, usually neurons, for long periods and retain the ability to replicate.

    · For example, a child who has recovered from chickenpox (varicella) will still have the virus in a latent form.

    · Years or decades later, the virus may be reactivated as a result of stress and/or physical factors.

    · This adult disease, which is very painful, is called shingles (zoster).

    · 11 of more than 100 genes of the herpesvirus genome are known to be involved in latency.

Pathogenesis of Human Herpes Type 1 to 5

Human Herpes Type

Name

Target cell Type

Disease

Latency

Transmission

1

Herpes simplex-1 (HSV-1)

Mucoepithelia

Oral herpes, encephalitis

Neuron

Close contact

2

Herpes simplex-2 (HSV-2)

Mucoepithelia

Genital and neonatal herpes, meningoencephalitis

Neuron

Close contact usually sexual

3

Varicella Zoster virus (VZV)

Mucoepithelia

Chickenpox (varicella) and Zoster (shingles)

Neuron

Contact or respiratory route

4

Epstein-Barr Virus (EBV)

B lymphocyte, epithelia

Infectious mononucleosis and Burkitt’s lymphoma; linked to Hodgkin’s disease, B cell lymphomas and to nasopharyngeal cancer.

B lymphocytes

Saliva

5

Cytomegalovirus (CMV)

Epithelia, monocytes, lymphocytes

Acute febrile illness; infections in immunosuppressed patients, leading cause of birth defects.

Monocytes, lymphocytes and possibly others

Contact, blood transfusions, transplantation, congenital

Clinical Features

HSV-1: Typically, Herpes labialis—Cold scores; Blisters around the mouth which lasts for around 1 week or more. May also affect the eyes (keratoconjunctivitis).

http://pathmicro.med.sc.edu/virol/coldsore2.jpg

HSV-2: Genital herpes, which is characterized by blisters, burning sensation and discharge.

VZV: In varicella, fever and malaise occur. Lesions appear on the trunk and spreads to the head and extremities. This is dangerous in pregnant women and may affect the nervous system—Guillain Barre syndrome. In zoster, painful vesicles occur along the course of a sensory nerve of the head or trunk.

http://pathmicro.med.sc.edu/virol/chickenpox3.jpg

Laboratory Diagnosis

    · Virus culture

    · Enzyme-linked immunosorbent assays (ELISAs)

    · Blood test

    · Tzanck smear

    · PCR assay

Epidemiology

HSV-1: Almost 100% of the adult population due to kissing and close proximity.

HSV-2: Up to 20% of the U.S. population due to sexual contact.

VZV: Varicella is a highly contagious disease of childhood; more than 90% of people in the U.S. have antibody by age 10 years. Varicella occurs worldwide.

EBV: Almost 100% of the adult population due to kissing and close proximity.

Control

HSV-1, HSV-2 and EBV: Avoid kissing to prevent contact with vesicular lesions or ulcers, and refrain from risky sexual behaviour. For the Herpes Simplex Viruses, caesarean section is recommended for women who are at term and who have genital lesions or positive viral cultures.

VZV: Vaccination with live, attenuated VZV (e.g. Varivax), and avoiding infected people.

Specific Viral Families: Hepadnaviridae


Hepadnaviridae

    · Small, enveloped, dsDNA (partially ssDNA) viruses.

    · The name hepadna comes from the infection of the liver—hepatitis—by a DNA virus.

    · Hepadnaviruses can cause chronic liver infections in humans and other animals, including ducks. In humans the hepatitis B virus causes hepatitis B, which can progress to liver cancer.

Hepatitis B Virus


http://pathmicro.med.sc.edu/lecture/hepatitis.gif

Important properties

  · 42-nm enveloped virion

    · Icosahedral nucleocapsid core contains a partially double-stranded circular DNA genome.

    · Envelope contains a protein called the surface antigen (HBsAg).

    · Core antigen (HBcAg) and the e antigen (HBeAg) are both located in the nucleocapsid protein but are antigenically different.

    · Endogeneous DNA-dependent DNA polymerase within the core.

    · Use of overlapping reading frame (ORF).

    · RNA-dependent DNA synthesis during replicative cycle.

Pathogenesis

    · Acute or chronic liver infection depending on the age at infection.

    · 90% of neonates and 50% of young children become chronically infected.

    · Only about 5% to 10% of immune-competent adults infected with HBV develop chronic hepatitis B.

    · A chronic carrier is someone who has HBsAg persisting in their blood for at least 6 months.

    · A high rate of heptatocellular carcinoma occurs in chronic carriers.

Basic characteristics of Hepatitis B infection:

Incubation period

60-90 days*

Fatality rate

1%

Recovery Rate

90%

Rate of Chronic Infection

<10%**

*with a range of 45-120 days

**although this can approach 90% in babies infected with HBV at birth.


http://www.medscape.com/content/2004/00/47/14/471470/art-jvh471470.fig2.gif

Above: The natural history of Hepatitis B

Clinical Features

Acute

    · Loss of appetite, nausea, vomiting, fever, abdominal pain and jaundice

    · About 90% - 95% of adults recover without sequelae

    · 5% - 10% become chronically infected

Chronic

    · While some chronic carriers will show clinical symptoms, most are asymptomatic—

they show no symptoms and may show no abnormalities on laboratory testing but remain infectious.

    · Some chronic carriers have chronic active hepatitis. This can lead to cirrhosis (the inflammation and hardening of the liver), hepatocellular carcinoma (primary liver cancer), and death.

http://www.pathology.med.ohio-state.edu/paxit/deptbase/Paxit/Images/10534/PAXIT025.JPG

http://www.stanford.edu/group/virus/hepadna/2004tansilvis/liver%20cirrhosis.gif

Laboratory Diagnosis


    · Quick detection for early HBV infection: immunoassay for HBsAg

    · HBsAg appears during the incubation period and is dewtectable in most patients during the acute disease. It falls to undetectable levels during convalescence in most cases

    · Prolonged presence of HBsAg indicates the carrier state and the risk of chronic hepatitis and hepatic carcinoma.

    · HBeAg is also detectable in acute infection which is characterized by a high rate of viral replication.

    · IgM antibodies against core antigen are detectable in serum.

    · Seubsequently, IgG antibodies against core are produced, and persist for life.

    · If the diagnosis of hepatitis B is confirmed, a prognosis may be assessed by liver biopsy.

Transmission

    · Through contaminated blood.

    · Sexual intercourse with an infected person. (horizontal transmission)

    · Perinatally from infected mother to newborn. (vertical transmission)

Epidemiology and Control

http://www.dshs.state.tx.us/idcu/disease/hepatitis/hepatitis_b/faqs/hepbdstb.gif

    · Estimated 400 million people worldwide infected with HBV.

    · Post 1987 babies all vaccinated against HBV.

    · Pre 1987 screening ongoing.

    · People at risk

o Doctors, laboratory workers, personnel coming in contact with blood.

o Drug addicts who share needles.

o Promiscuous behaviour.

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