Adenovirus attaches to host-cell receptor with its glycoprotein fibers and enters via endocytosis. After uncoating in the cytoplasm, in which the outer capsid is removed, the viral core containing the genome and associated histones is transported to the nucleus. One unique feature of adenovirus is that its penton protein has a toxic effect on cells.
Transcription of both strands of viral DNA by cellular RNA polymerase is temporally regulated and leads to formation of early and late mRNAs, coding for early and late proteins. Primary transcripts are capped, polyadenylated, and spliced.
About 12 non-structural proteins are formed early, before the genome is replicated. The actions of these early proteins include blocking the ability of the p53 and Rb growth suppressor genes to suppress cell division and inhibiting apoptosis in the host cell. The viral structural proteins are synthesized late, after DNA replication. Other late proteins alter aspects of cellular structure and metabolism to ensure efficient virus assembly and release. New virus particles are assembled in the nucleus, and mature viruses are released by lysis of the host cell.
As viral synthesis increases, the synthetic machinery of the host cell is progressively shut down. Host cell DNA synthesis is shut off early in the viral replication cycle, and host cell RNA and protein synthesis is shut off later. The cell eventually dies.
The needs that human adenovirus has in order
to interact successfully with the host cell requires that the cell remain functional
for a long period after infection. Hence, cytopathology and cell death are slow.
Human adenovirus synthesizes VA RNA, a short structured RNA molecule that inhibits
the cell’s ability to produce interferon. This strategy keeps the host
cell from mounting defenses against viral gene expression and allows the virus
to remain associated with the host for long periods of time as a persistent
infection, especially in the epithelium of adenoidal tissue and the lungs. Portions
of viral DNA persist in host cells after viral replication has stopped as either
a circular extra chromosome or by integration into host DNA. This persistence
may be important in the pathogenesis of adenovirus infection sequelae that include
Swyer-James syndrome, permanent airways obstruction, bronchiectasis, bronchiolitis,
obliterans, and steroid-resistant asthma.