Adenovirus Flashcards
Adeno structure, Baltimore, groups
Adenoviridae
NON enveloped dsDNA, Group 1, subgroup/species A to G
Adeno receptor
The fiber protein from most adenoviruses, except species B, binds to the cellular receptor CAR (coxsackie-adenovirus receptor), which also binds coxsackie B virus [2]. Group B adenoviruses have been shown to bind to CD46, a complement-related protein (also HHV6 receptor)
infect human epithelial cell lines, exhibiting a characteristic cytopathic effect
Adeno latency
Adenoviruses can be detected in long-term cultures of tonsillar tissue and have been shown to persist in CD4+ T cells isolated from tonsils [30]. Adenoviral DNA is also highly prevalent in intestinal lymphocytes.
Important serotypes Adeno
B 11,34,35 - haemorrhagic cystitis
D 8,19, 37 - keratoconjunctivitis
F 40 & 41 - GI
Adeno clinical syndromes
- URTI
- LRTI & bronchiolitis
- Otitis media
- Epidemic keratoconjunctivitis (EKC) is a more serious disease associated primarily with the species D serotypes 8, 19, and 37. It is characterized by bilateral conjunctivitis with preauricular adenopathy, followed by the development of painful corneal opacities.
- GI disease
- Hepatitis
- Acute haemorrhagic cystitis
- Meningitis & encephalitis
- Disseminated
- Myocarditis
2022 Adeno/AAV outbreak
In early 2022, an outbreak of acute hepatitis was identified among young children (most <5 years) in the United Kingdom and Ireland, and other clusters with similar characteristics were subsequently reported in at least 35 countries. A systematic review of 22 case series and case-control studies identified 1643 cases of acute hepatitis of unknown etiology in children, among whom 7.3 percent required liver transplantation and 1.5 percent died.
adenovirus (primarily type 41) was the pathogen most commonly detected by PCR in the United Kingdom (142/216 tested), sometimes with other common pediatric viruses (eg, rhinovirus, enterovirus, influenza virus, SARS-CoV-2). In addition, adenovirus was detected in 100 (44.6 percent) of 224 cases tested in the United States.
Preprints (nonpeer reviewed studies) from the United Kingdom suggest that coinfection with adeno-associated virus 2 (AAV2) may play a role [123,124]. Using genomic methods, AAV2 DNA (and ribonucleic acid [RNA]) was detected in the liver of 9 of 9 cases and the blood of 25 of 26 children with acute unexplained hepatitis; adenovirus and human herpesvirus 6B were also detected in most children. In contrast, AAV2 was not detected in most controls, including children with adenovirus who had normal liver function. AAV2 is a member of the parvovirus family that often accompanies adenovirus but is not known to cause disease. It cannot replicate without a helper virus (eg, adenovirus, herpesvirus).
Adeno treatment
- First line: Cidofovir has been the antiviral agent most frequently used to treat adenovirus infections, but severe nephrotoxicity is a major dose-limiting toxicity. WITH PROBENECID
- Brincidofovir, an experimental lipid ester of cidofovir that has lower potential for nephrotoxicity than cidofovir, is being studied for adenovirus
Cidofovir: 5 mg/kg once weekly for 2 weeks for induction followed by 5mg/kg once every 2 weeks
- Second line: T cells
Unproven:
- Ganciclovir
- Ribavirin
- IVIG
- Virus specific T cells
Adeno vaccine
Live oral vaccine ONLY for US military.
Serotypes 4 &7.
Ages 17 to 50.
Severe adeno risk factors
- HSCT
- T cell depletion
- Total lymphocytes < 200/microL
- Allo HSCT with unrelated donor or cord blood
- Severe GVHD
- Young age
- Alemtuzumab
Define probable vs proven disseminated Adeno DISEASE
Probable: Adv detection + compatible clinical syndrome but NO histological confirmation
Proven: above + Histological confirmation
Adeno monitoring in HSCT
Adeno PCR on blood weekly if risk factors - see otherwise card
Stool & urine PCR can also be used
Adeno diagnostics
Including HPE
Grape like clusters cytopathological effects
Histology - smudge cells
