8.4 Other clinically important DNA viruses

DNA viruses are diverse pathogens causing a range of clinical manifestations. This section explores less common but clinically significant DNA viruses, including parvoviruses, herpesviruses, polyomaviruses, and poxviruses. These pathogens can cause severe complications, especially in immunocompromised individuals.

Understanding the structure, replication strategies, and clinical presentations of these viruses is crucial for effective diagnosis and management. While some infections are self-limiting, others require specific treatments or careful monitoring, highlighting the importance of recognizing these less common but potentially serious viral pathogens.

Less Common DNA Viruses

Parvovirus and Bocavirus

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• Parvovirus B19 causes erythema infectiosum (fifth disease) with potential severe consequences in immunocompromised individuals or pregnant women
  • Single-stranded DNA genome
  • Replicates in rapidly dividing erythroid progenitor cells
  • Transmitted through respiratory droplets and blood products
  • Presents with "slapped cheek" rash and can lead to aplastic crisis in patients with chronic hemolytic anemia
  • Diagnosis made through serological testing or PCR
• Human bocavirus (HBoV) associates with respiratory tract infections and gastroenteritis, particularly in young children
  • Small, non-enveloped virus with single-stranded DNA genome
  • Replicates in respiratory and gastrointestinal epithelial cells
  • Transmitted through respiratory secretions and fecal-oral route
  • Presents as upper and lower respiratory tract infections or gastroenteritis
  • Diagnosis made through PCR of respiratory or stool samples

Herpesviruses and Polyomaviruses

• Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) associate with roseola infantum and other clinical manifestations
  • Double-stranded DNA viruses establishing latency in T lymphocytes
  • Transmitted through saliva and close personal contact
  • Often result in roseola infantum with high fever followed by distinctive rash
  • Diagnosis made through PCR of blood or cerebrospinal fluid, or by serology
• JC virus and BK virus (polyomaviruses) cause severe complications in immunocompromised individuals
  • Circular, double-stranded DNA genomes replicating in host cell nuclei
  • Widespread in population, reactivating during immunosuppression
  • JC virus causes progressive multifocal leukoencephalopathy (PML) with neurological symptoms (cognitive impairment, motor dysfunction)
  • BK virus causes nephropathy in transplant recipients, leading to graft dysfunction
  • JC virus diagnosed through MRI and PCR of cerebrospinal fluid
  • BK virus diagnosed through PCR of urine and blood, and renal biopsy in some cases

Poxvirus

• Molluscum contagiosum virus (MCV) causes benign, self-limited skin lesions, problematic in immunocompromised patients
  • Large, complex double-stranded DNA genome
  • Replicates in epidermal keratinocytes
  • Transmitted through direct skin contact or fomites
  • Presents as small, flesh-colored, dome-shaped papules with central depression
  • Diagnosis typically clinical, biopsy performed for confirmation

Structure and Replication of DNA Viruses

Genomic Characteristics

• Parvovirus B19 and Human bocavirus possess single-stranded DNA genomes
  • Compact genomes with limited coding capacity
  • Rely heavily on host cell machinery for replication
• HHV-6, HHV-7, JC virus, and BK virus contain double-stranded DNA genomes
  • Larger genomes allowing for more complex replication strategies
  • Encode many of their own enzymes for DNA replication
• Molluscum contagiosum virus has a large, complex double-stranded DNA genome
  • Encodes numerous genes involved in virus-host interactions and immune evasion

Replication Strategies

• Parvovirus B19 replicates in rapidly dividing erythroid progenitor cells
  • Requires actively dividing cells due to limited coding capacity
  • Utilizes host cell DNA polymerase for genome replication
• HHV-6 and HHV-7 establish latency in T lymphocytes
  • Employ a biphasic replication cycle with lytic and latent phases
  • Latent phase allows for long-term persistence in the host
• JC and BK viruses replicate in the nucleus of host cells
  • Utilize host cell machinery for genome replication and transcription
  • Produce viral proteins that alter cell cycle regulation
• Molluscum contagiosum virus replicates in epidermal keratinocytes
  • Induces cellular proliferation and differentiation
  • Produces inclusion bodies containing viral particles

Clinical Manifestations of DNA Virus Infections

Cutaneous and Systemic Manifestations

• Parvovirus B19 causes erythema infectiosum with "slapped cheek" rash
  • Can lead to aplastic crisis in patients with chronic hemolytic anemia
  • May cause hydrops fetalis in pregnant women
• HHV-6 and HHV-7 infections result in roseola infantum
  • High fever followed by distinctive rash (exanthem subitum)
  • Can cause febrile seizures in young children
• Molluscum contagiosum presents as characteristic skin lesions
  • Small, flesh-colored, dome-shaped papules with central depression
  • Lesions can be widespread in immunocompromised individuals

Respiratory and Gastrointestinal Manifestations

• Human bocavirus infections present as respiratory tract infections
  • Associated with wheezing and asthma exacerbations in children
  • Can cause bronchiolitis and pneumonia
• Human bocavirus also linked to gastroenteritis
  • Presents with diarrhea, vomiting, and abdominal pain
  • Often occurs concurrently with respiratory symptoms

Severe Complications in Immunocompromised Patients

• JC virus causes progressive multifocal leukoencephalopathy (PML)
  • Presents with cognitive impairment and motor dysfunction
  • Can lead to severe neurological deficits and death
• BK virus causes nephropathy in transplant recipients
  • Results in graft dysfunction and potential graft loss
  • Can also cause hemorrhagic cystitis in stem cell transplant recipients

Treatment and Prevention of DNA Virus Infections

Antiviral Therapies and Supportive Care

• Parvovirus B19 and Human bocavirus lack specific antiviral treatments
  • Management focuses on supportive care and symptom relief
  • Intravenous immunoglobulin used in severe cases of parvovirus B19 infection
• HHV-6 and HHV-7 infections generally self-limiting in immunocompetent individuals
  • Ganciclovir or foscarnet used in severe cases or immunocompromised patients
  • Antiviral therapy may be necessary for HHV-6 encephalitis
• JC virus treatment involves immune reconstitution or reduction of immunosuppression
  • No specific antiviral therapy available for PML
  • Experimental approaches include cytarabine and cidofovir
• BK virus management primarily involves reducing immunosuppression in transplant recipients
  • Cidofovir or leflunomide used in some cases of BK virus nephropathy
  • Careful monitoring of viral load guides treatment decisions

Prevention Strategies

• Hygiene measures crucial for preventing transmission of these DNA viruses
  • Hand washing and respiratory etiquette (covering mouth when coughing or sneezing)
  • Avoiding close contact with infected individuals
• No vaccines currently available for these less common DNA viruses
  • Research ongoing for potential vaccine development (parvovirus B19, HHV-6)
• Screening and monitoring important for high-risk populations
  • Regular PCR testing for BK virus in kidney transplant recipients
  • Neurological monitoring for PML in patients on certain immunosuppressive therapies

Management of Skin Lesions

• Molluscum contagiosum lesions often resolve spontaneously
  • Treatment options include cryotherapy and curettage
  • Topical medications such as imiquimod or podophyllotoxin used in some cases
• Prevention of molluscum contagiosum spread
  • Avoiding direct contact with lesions
  • Proper hygiene and avoiding sharing personal items (towels, clothing)