• Antiadenovirus is a cocktail of mouse monoclonal antibodies derived from cell culture supernatant
• Though there are numerous genera within the Adenoviridae family, the antigen targeted (group specific hexon antigen) in commercially available antiadenovirus cocktails has been selected to detect all known, clinically important adenovirus serotypes

• Antiadenovirus is a cocktail of mouse monoclonal antibodies with nuclear and cytoplasmic staining pattern developed to detect all known serotypes of adenovirus
• False positives are extremely uncommon
• Most false negatives (cases with positive viral cytopathic effect and negative IHC) result from exhaustion of the diagnostic tissue

• Double stranded, nonenveloped DNA viruses with a single, nonsegmented linear genome capped by covalently bound terminal proteins at either end of the genome
• Adenovirus produces nuclear inclusions without cytomegaly
• Virus binds to coxsackie adenovirus receptor, CD46 (complement regulatory protein), desmoglein 2 or sialic acid (primary receptor used depends on the viral serogroup), followed by viral internalization (Rev Med Virol 2009;19:165, Nat Med 2011;17:96)
• Viral replication cycle takes ~32 - 36 hours and up to 10,000 virions can be produced; new virions remain in the cell until it degenerates and lyses (Tille: Bailey & Scott's Diagnostic Microbiology, 13th Edition, 2013)

• Nuclear and cytoplasmic
• False positives are extremely uncommon
• Most false negatives (cases with positive viral cytopathic effect and negative IHC) result from exhaustion of the diagnostic tissue (Am J Clin Pathol 2017;147:96)
• Other limitations of this and other IHC tests are fixation time of tissues, dilution factor of antibody, retrieval method utilized and incubation time; optimal performance should be established through positive and negative controls

Contributed by Vikas Mehta, M.D., Maria M. Picken, M.D., Ph.D. and Cullen Lilley, M.S., M.A.

Contributed by Maria M. Picken, M.D., Ph.D.

• Kidney, needle core biopsy:
  • Adenovirus nephritis (see comment)
  • Comment: Renal parenchyma with necrotizing tubulointerstitial nephritis is consistent with adenovirus nephritis. Immunohistochemical stain for adenovirus shows nuclear and cytoplasmic expression in affected cells.

• Liver, needle core biopsy:
  • Adenovirus hepatitis (see comment)
  • Comment: Liver parenchyma with necrotizing hepatitis is consistent with adenovirus hepatitis. Immunohistochemical stain for adenovirus shows nuclear and cytoplasmic expression in affected cells.

• Emerg Infect Dis 2010;16:769, J Clin Microbiol 2006;44:3371

What is the immunohistochemical staining pattern of adenovirus in adenovirus nephritis?

1. Cytoplasmic
2. Dot-like
3. Nuclear
4. Nuclear and cytoplasmic

D. Nuclear and cytoplasmic. Of the choices listed, nuclear and cytoplasmic staining is seen in IHC for adenovirus. However, a virus specific diagnosis cannot be made based on the pattern of stain alone, as other stains can show nuclear and cytoplasmic staining. For example, diffuse and strong nuclear or nuclear and cytoplasmic staining involving the basal and parabasal layers of squamous epithelium is seen in p16 testing for HPV (block-like staining). Thus, the diagnosis is based on the antibody specificity while the pattern of stain is helpful. Moreover, the type of infected cell can be helpful in the differential diagnosis (e.g., CMV typically infects endothelium while adenovirus infects epithelial cells, as illustrated in this topic). Cytoplasmic stain is typically seen in IHC for several keratins or other intracytoplasmic proteins; stain for CK20 in Merkel cell carcinoma is an exception. Dot-like stain is typically seen for CK20 in Merkel cell carcinoma. Nuclear stain is positive in IHC for polyoma virus.

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Reference: Adenovirus