8.3 Adenoviruses and poxviruses

Adenoviruses and poxviruses are two distinct families of DNA viruses that cause different diseases in humans. Adenoviruses typically lead to respiratory and eye infections, while poxviruses cause skin lesions and systemic illness.

These viruses differ in structure, replication, and how they spread in the body. Understanding their unique characteristics helps us grasp how they cause disease and how we can prevent and treat infections.

Adenovirus and Poxvirus Structure

Structural Characteristics

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• Adenoviruses possess non-enveloped, icosahedral capsids with double-stranded DNA genomes
• Poxviruses feature large, complex, enveloped structures containing double-stranded DNA genomes
• Adenovirus capsids comprise hexon and penton proteins with fiber proteins extending from penton bases
• Poxviruses exhibit a complex structure including a dumbbell-shaped core housing the genome and lateral bodies
• Adenovirus capsid diameter measures approximately 90-100 nm
• Poxvirus dimensions range from 200-400 nm in length and 170-260 nm in width (variola virus)

Replication Cycle Comparison

• Adenovirus replication occurs entirely within the nucleus
  • Involves distinct early and late gene expression phases
  • Utilizes protein-primed mechanism for DNA replication
• Poxvirus replication takes place in the cytoplasm
  • Employs virus-encoded enzymes for replication processes
  • Uses unique rolling hairpin mechanism for genome replication
• Adenovirus assembly happens in the nucleus
• Poxviruses form immature virions in cytoplasmic viral factories
• Adenovirus release occurs through cell lysis
• Poxviruses exit cells via budding or cell lysis depending on strain and host cell type

Adenovirus vs Poxvirus Infections

Clinical Manifestations

• Adenovirus infections primarily cause respiratory symptoms, conjunctivitis, and gastroenteritis
  • Respiratory infections range from mild upper respiratory tract illness to severe pneumonia (immunocompromised patients)
  • Conjunctivitis presents as red, swollen eyes with discharge
• Poxvirus infections mainly result in characteristic skin lesions
  • Lesions progress through stages macules, papules, vesicles, pustules, and scabs
  • Timing and appearance vary among different poxvirus species (smallpox, monkeypox)
• Both infections can produce systemic symptoms fever, malaise, and lymphadenopathy
  • Generally more severe in poxvirus infections

Complications and Severity

• Adenovirus complications may include myocarditis and meningoencephalitis
  • Severe cases observed in immunocompromised individuals or specific serotypes
• Poxvirus infections can lead to secondary bacterial infections and organ failure
  • Mortality rates vary depending on virus species and host factors
• Adenovirus-induced pneumonia potentially fatal in immunocompromised patients
• Poxvirus ocular infections risk corneal scarring and blindness
  • More severe than adenovirus conjunctivitis

Pathogenesis and Immunity of Adenoviruses and Poxviruses

Infection and Spread

• Adenoviruses primarily infect and replicate in epithelial cells
  • Target respiratory tract, eyes, and gastrointestinal system
• Poxviruses initially infect epidermal cells
  • Spread to regional lymph nodes and other organs
• Both viruses employ mechanisms to evade host immune responses
  • Produce immunomodulatory proteins interfering with innate immune signaling pathways
  • Examples adenovirus VA RNA inhibits PKR activation, poxvirus A46R protein blocks TLR signaling

Immune Response

• Innate immune response involves type I interferon production and activation of natural killer cells and macrophages
  • Interferon-alpha and interferon-beta crucial for initial viral control
• Adaptive immunity includes both humoral and cell-mediated responses
  • Neutralizing antibodies play a vital role in preventing reinfection
  • IgA antibodies important for mucosal immunity (adenovirus)
• T cell responses, particularly CD8+ cytotoxic T lymphocytes, essential for clearing virus-infected cells
  • CD4+ T helper cells support antibody production and CD8+ T cell function
• Long-lasting immunity generally established following recovery
  • Duration and strength of protection may vary between virus families
  • Cross-reactive immunity observed among some adenovirus serotypes

Epidemiology and Control of Adenovirus and Poxvirus Outbreaks

Transmission and Distribution

• Adenovirus infections occur worldwide, affecting all age groups
  • Certain serotypes associated with specific clinical syndromes and age groups (serotype 14 severe respiratory disease in adults)
• Poxvirus infections have varying geographic distributions and host ranges
  • Smallpox eradicated globally in 1980
  • Monkeypox endemic in Central and West Africa, recent outbreaks in non-endemic countries
• Adenovirus transmission primarily through respiratory droplets, fecal-oral route, and contact with contaminated surfaces
  • Outbreaks common in closed settings (military barracks, schools)
• Poxviruses typically spread through direct contact with infected individuals or animals
  • Zoonotic transmission observed in some species (monkeypox)

Prevention and Control Measures

• Adenovirus outbreak control includes proper hand hygiene, respiratory etiquette, and surface disinfection
  • Chlorine-based disinfectants effective against adenoviruses
• Poxvirus outbreak management relies on early detection, isolation, contact tracing, and ring vaccination
  • Ring vaccination strategy successfully used in smallpox eradication
• Vaccination available for some adenovirus serotypes and smallpox/monkeypox
  • Adenovirus vaccine types 4 and 7 used in U.S. military
  • Modified Vaccinia Ankara (MVA) vaccine approved for smallpox and monkeypox prevention
• Antiviral drugs used in severe cases or post-exposure prophylaxis
  • Cidofovir for adenoviruses
  • Tecovirimat for poxviruses
• Surveillance and reporting systems crucial for early outbreak detection and response
  • Global Smallpox Laboratory Network monitors for potential poxvirus reemergence