Medical Microbiology: Human Herpes Virus 5 (Cytomegalovirus)

Overview of Human Herpes Virus 5 (HHV5)

• HHV5 is a common human pathogen, also known as Cytomegalovirus (CMV)
• Belongs to the herpesvirus family and is the most common viral cause of congenital defects
• Usually causes mild or asymptomatic disease in children and adults, but is an opportunistic pathogen in immunocompromised patients

Structure and Replication

• CMV is a herpesvirus, an enveloped double-stranded DNA virus
• Cells permissive for CMV replication: fibroblasts, epithelial cells, granulocytes, and macrophages

Epidemiology

• CMV is common worldwide
• Virus is transmitted through:
  • Oral and sexual contact
  • Blood transfusions
  • Tissue transplants (especially kidneys and bone marrow)
  • In utero, at birth, and through breastfeeding
  • All secretions (urine, saliva, semen, cervical secretions, breast milk, and tears)

Who Is at Risk?

• Fetuses of mothers who get infected/reactivate during pregnancy
• Sexually active people
• Blood and organ recipients
• Immunocompromised people

Pathogenesis and Immunity

• CMV establishes persistent and latent infections rather than extensive lytic infections
• Highly cell-associated and spreads throughout the body within infected cells, especially lymphocytes and leukocytes
• Virus establishes latency in hematopoietic progenitor cells in the bone marrow and monocytes
• Reactivates on immunosuppression and possibly by allogeneic stimulation
• CMV is shed sporadically throughout life

Clinical Manifestations

• CMV disease is an opportunistic disease, rarely causing symptoms in the immunocompetent host
• Congenital infection:
  • May lead to hearing, eyesight, and intelligence deficits
  • Common infectious causes of congenital hearing loss
  • Vision loss and mental retardation are also common consequences
• Infection in children and adults:
  • CMV is widely prevalent
  • Sexually transmitted
  • Asymptomatic, but may show a heterophile-negative mononucleosis syndrome
• Infection in the immunocompromised host:
  • CMV is a prominent opportunistic infectious agent
  • Causes symptomatic primary or recurrent disease
  • CMV disease of the lung is a common outcome in immunosuppressed patients and can be fatal if not treated

Laboratory Diagnosis

• Histology:
  • Histologic hallmark of CMV infection is the “owl’s eye”
  • Found in any tissue and in urine
• Serology:
  • Not reliable except if seroconversion is documented in primary infection
  • Useful for screening blood donations
• Detection of viral antigen or genome:
  • Rapid, sensitive diagnosis can be obtained by detection of viral antigen or genome
  • Using immunofluorescence, ELISA, or PCR in cells of a biopsy, blood, bronchoalveolar lavage, or urine sample
• Culture of virus in fibroblast cell lines and observation of the characteristic cytopathic effects

Treatment

• FDA approved for treatment of immunosuppressed patients:
  • Ganciclovir
  • Valganciclovir
  • Cidofovir
  • Foscarnet

Control

• CMV spreads through:
  • Sexual contact
  • Tissue transplantation
  • Transfusion
• Spread by these means is preventable
• Use of condoms or abstinence would limit viral spread
• Screening of potential blood and organ donors for CMV seronegativity

Human Herpesviruses 6 and 7

• HHV-6 is a herpesvirus that was first isolated from the blood of patients with AIDS
• Similar to CMV, HHV-6 is lymphotropic and ubiquitous
• Causes a common disease of children, Exanthem Subitum (roseola)
• HHV-7 was isolated from the T cells of a patient with AIDS who was also infected with HHV-6

Pathogenesis and Immunity of HHV-6 and HHV-7

• HHV-6 infection occurs very early in life
• Virus replicates in the salivary gland, is shed, and is transmitted in saliva
• HHV-6 primarily infects lymphocytes, especially CD4 T cells
• Establishes a latent infection in hematopoietic progenitor cells and T cells
• Replication of HHV-6 is controlled by cell-mediated immunity

Clinical Syndromes of HHV-6 and HHV-7

• Exanthem subitum, or roseola, is caused by either HHV-6 or HHV-7
• Characterized by the rapid onset of high fever, followed by a rash on the trunk and face, and then spreads and lasts only 24 to 48 hours
• Virus establishes a lifelong latent infection of T cells
• HHV-6 is the most common cause of febrile seizures in childhood (aged 6 to 24 months)