Infection and Immunity Module: Herpesviruses

Infection and Immunity Module

• This module covers infections and immunity
• Dr. Ibrahim Naqid is the lecturer
• The module is offered at Zakho Medical College, University of Zakho

Herpesviruses

• Herpesviruses are widely distributed
• Eight human herpesviruses have been identified
  • Herpes simplex virus 1 & 2
  • Varicella-zoster virus
  • Epstein-Barr virus
  • Human cytomegalovirus
  • Human herpesviruses 6 to 8

Biological properties

• Herpesviruses are DNA viruses
• All herpesviruses encode enzymes needed for viral replication
• Viral replication destruction of host cells
• All establish latent infections that last the host's lifetime

Structure

• Nucleocapsid surrounded by a lipid envelope
• Prefer mucosal surfaces

Transmission

• Those transmitted by oral secretions are common in children, with high seroprevalence
• Those transmitted by genital secretions are common in adolescence, with lower seroprevalence

What is latency?

• Virus remains dormant within host cells
• The virus is not actively replicating or causing symptoms but persists.

Terms

• Primary infection: First infection with a virus
• Latency: Virus remains dormant within cells
• Recurrent infection: Recurrence of symptoms -HSV 1 & 2 - neurons -VZV (HHV-3) – dorsal root ganglia -EBV (HHV-4) - B cells -CMV – bone marrow

Clinical Presentation

• Herpes viruses can integrate their genetic material onto host cells.
• Some herpesviruses have oncogenic potential in both animals and humans, including lymphoproliferative disorders
• Primary infection with human herpesviruses is generally mild or subclinical, especially in immunocompetent hosts, sometimes presenting with a rash or skin eruption.
• In immunocompromised hosts, primary herpesvirus infection can present with severe, life-threatening illness.
• Factors influencing clinical presentation: -Host-pathogen interactions -Immune status of the host -Affected organ
• Different tissue tropisms: •CMV-retina and GIT •VZV-lung tissue •HSV-encephalitis

International Names of Herpes Viruses

• HHV-1: Herpes simplex 1 – Alphaherpesvirinae – Short replication cycle – Cytolytic
• HHV-2: Herpes simplex 2 – Alphaherpesvirinae – Short replication cycle – Cytolytic
• HHV-3: Varicella-Zoster – Alphaherpesvirinae – Latent Sensory ganglia
• HHV-4: Epstein-Barr virus – Gammaherpesvirinae – Latency in T or B cells
• HHV-5: Cytomegalovirus – Betaherpesvirinae – Restricted Host range – Long replication cycle
• HHV-6: HHV-6 – Betaherpesvirinae – Cytomegalic
• HHV-7: HHV-7 – Betaherpesvirinae – Long replication cycle – Cytomegalic
• HHV-8: Kaposi's Sarcoma Virus – Gammaherpesvirinae– Latency in T or B cells

Alphaherpesviruses

• HSV-1
• HSV-2
• HSV-3

HSV-1 and HSV-2

• Worldwide distribution and endemic in humans
• HSV-1: Primary infection through oropharyngeal secretions (95% seropositive by age 5)
• HSV-2: Transmitted through sexual contact (10-30% seropositive in adults)
• Causes various diseases:
  • Herpes skin rashes
  • Herpes simplex stomatitis
  • Herpes simplex eye infection (red, swollen eye)
  • Encephalitis (brain inflammation)

Varicella-Zoster Virus (VZV)

• Endemic in most populations
• Primarily transmitted via respiratory route
• 10% of the population remains uninfected

Chickenpox (Varicella)

• Vesicular skin rash starting on body and head, becoming itchy, often healing without scarring.

Shingles (Herpes Zoster)

• Painful skin rash, with vesicles limited to a dermatome (area of skin supplied by a single spinal nerve).

Betaherpesviruses

• Human CMV (Cytomegalovirus)
• Human Herpesvirus 6 & 7

Cytomegalovirus (CMV)

• Transmitted via person-to-person contact
  • Close contact
  • Saliva
  • Sexual contact
  • Perinatally
  • Organ transplant
  • Blood transfusion
• Clinical course:
  • Self-limiting disease usually doesn't need treatment
  • Can cause serious problems in people with deficient immune systems
  • AIDS patients
  • Transplant patients
  • Pregnancy
  • Can cause colitis, retinitis, pneumonitis, etc

Gammaherpesviruses

• Epstein-Barr Virus (EBV)
• Kaposi's Sarcoma-Associated Herpesvirus (KSHV or HHV-8)

Epstein-Barr Virus (EBV)

• Spread through droplets
• Causes infectious mononucleosis (glandular fever)
• Other diseases:
  • African lymphoma
  • Nasopharyngeal carcinoma
  • B-cell lymphoma

Infectious Mononucleosis

• Symptoms: Extreme fatigue, fever, sore throat, swollen lymph nodes, and sometimes swollen liver or spleen and rash.
• Diagnostics: Monospot test, helpful but not definitive; further testing is sometimes necessary to confirm the presence of EBV
• Distinguished from other mononucleosis cases- EBV mononucleosis is caused by EBV
• Non-EBV mononucleosis is milder version caused by CMV

Diagnosis

• Clinical presentation
• Serology by ELISA (detects antibodies)
• Molecular by PCR (detects viral DNA)
• Histopathology (tissue studies)
• For CMV: blood sample, urine, saliva, or other body tissues to detect the virus or antibodies

Treatment

• Specific antiviral therapy
  • Acyclovir – HSV and VZV
  • Cidofovir – CMV and resistant HSV
  • Ganciclovir – CMV and EBV

Hepatitis Viruses

• Five hepatitis viruses are identified: -Hepatitis A
  • Hepatitis B
  • Hepatitis C
  • Hepatitis D
  • Hepatitis E
• Transmission and types:
• A & E are transmitted orally;
• B, C, D are transmitted vertically (sex and blood including contaminated needles)

HAV (Hepatitis A Virus)

• RNA virus
• Oral transmission
• Acute infection only.
• Vaccine available
• Endemic in most countries.
• Diagnosed through ELISA IgM test.
• Pathogenesis: Enters via gut, replicates in digestive tract and spreads to liver, multiplies in hepatocytes. Transient viremia (virus in blood), excretion in stool two weeks before onset of symptoms

HBV (Hepatitis B Virus)

• DNA virus
• Transmission: Mother-to-baby, sex, blood, blood products (contaminated needle, etc)
• Acute and chronic disease
• Vaccine available
• Diagnosed by ELISA, IgM and IgG.
• Pathogenesis: Parenterally transmitted, replicates in the liver, shed into the bloodstream, highly infectious.

HCV (Hepatitis C Virus)

• RNA virus
• Transmission: Mother-to-baby, sex, blood, blood products (contaminated needle, etc). Also from organ donation.
• Acute and chronic.
• Vaccine unavailable.
• Diagnosed through PCR test.

HDV (Hepatitis D Virus)

• RNA virus
• Defective virus needing HBV for replication.
• Transmission: Mother-to-baby, sex, blood, blood products (contaminated needle, etc).
• Acute and chronic

HEV (Hepatitis E Virus)

• RNA virus
• Oral transmission
• Acute infection only.
• Vaccine unavailable. Diagnosed by ELISA IgM and PCR for specific sequences in stool
• Pathogenesis similar to HAV

Clinical Features of Hepatitis

• Patients experience similar symptoms, especially in the acute stage
• Specific diagnosis is made through laboratory tests.
• Common symptoms include: anorexia, nausea, vomiting, right upper quadrant pain, raised liver enzymes (AST and ALT), jaundice. Anicteric cases are also very common.

Vaccine Availability

• Vaccines are available for Hepatitis A and B.