Adeno virus

• Human adenoviruses (HAdV) are a non-enveloped, linear, double-stranded DNA virus that infects epithelial cells of the respiratory and gastrointestinal tract, cornea, lymphoid tissues (tonsils, adenoids), and can cause respiratory illness, gastroenteritis, and conjunctivitis.
• HAdV8, HAdV19, HAdV37, HAdV40, HAdV41, HAdV2, HAdV5 are species of HAdV.
• HAdV infections are most commonly short-term acute infections, but can also cause enigmatic long-term persistent infections.
• HAdV infection is common in tonsillar diseases.
• HAdV classification includes species, types (serotypes/genotypes), major site of infection, and geographical distribution.
• HAdV has 7 species and >110 types based on serological and genome sequencing methods.
• HAdV structure includes major, minor & core proteins (broadly called as the “capsid proteins”).
• Major capsid proteins in HAdV structure are hexon, penton base, fiber, and minor capsid proteins are protein VI, protein IIIa, protein VIII, and protein IX.
• Core proteins in HAdV structure are terminal protein (TP), protein Mu, protein VII, protein V, and IVa2, and protease (AVP/p23) is a core protein.
• HAdV attachment to cell receptors involves the fiber knob binding to an attachment receptor (CAR, CD46, DSG-2, GD1a, polysialic acid) and the penton base binding to an integrin entry receptor (CAR).
• HAdV genome is linear dsDNA, genome size 30 - 40kbp.
• HAdV uses cellular receptors for attachment and entry.
• Early genes (E1A, E1B, E2, E3, E4) are enzymes and regulatory proteins.
• HAdV has major capsid proteins: hexon, penton base, and fiber.
• HAdV E1A protein is a multifunctional essential HAdV protein, expressed as the first viral protein in HAdV-infected cells, and does not bind to DNA, but interacts with many cellular transcription regulating proteins.
• 5’ ends of viral DNA contain viral TP protein.
• HAdV DNA has a chromatin-like structure in the virion.
• Viral pVII protein mimics cellular histones/nucleosomes.
• HAdV life cycle involves attachment, nuclear import, early phase gene expression, DNA replication, late phase gene expression, assembly, cell lysis/maturation, endocytosis + release of virion, and maturation.
• Intermediate genes (pIX, IVa2) are regulatory proteins.
• Proteins involved in nucleotide synthesis, DNA replication, etc., are involved in HAdV replication.
• HAdV is an icosahedral, nonenveloped particle.
• Late genes (MLTU) are structural proteins (+regulatory proteins).
• HAdV species-specific interactions with receptors involve the fiber knob binding to CAR, CD46, DSG-2, GD1a, polysialic acid, and the penton base binding to integrins.
• HAdV has protruding trimeric fibers needed for virus attachment.
• E1A protein contains 3 - 4 conserved regions (CRs), one of which, CR3, is missing in E1A-243R.
• anti-apoptotic protein Berk., 2005 is transcribed from the E1B transcription unit and locates into mitochondria, blocking oligomerisation of the pro-apoptotic Bax, Bak proteins, inhibiting apoptosis.
• One MLTU pre-mRNA gives rise to 5 different MLTU mRNA families: L1 mRNA to L5 mRNA.
• The transcription start site (TSS) is located at the MLTU promoter, (pA) is the polyadenylation site, G is the cap structure at 5’ of mRNA, (A)n is the poly(A) tail at the 3’ end of mRNA.
• Most MLTU mRNAs are expressed during the late phase, with the exception of L1.
• Alternative polyadenylation is a way to increase coding capacity, also known as genetic economy.
• Core proteins, Minor capsid proteins, Major capsid proteins are encoded by the MLTU promoter.
• The MLTU promoter encodes viral structural proteins and some regulatory proteins.
• MLTU has one promoter, many different mRNAs.
• The usage of 5 different polyadenylation sites (L1(pA) to L5(pA)) is a form of alternative polyadenylation.
• HAdV MLTU (Major Late Transcription Unit) is encoded by the virus structural proteins and some regulatory proteins.
• MLTU mRNAs undergo extensive modifications such as alternative polyadenylation and splicing.
• Therapeutic applications of HAdV include replication-deficient HAdV, which lacks or contains mutated E1A gene.
• HAdV infections cause diseases such as respiratory infections, conjunctivitis, and pneumonia.
• Adenovirus-based vaccines deliver the viral antigen (e.g. SARS-CoV-2 Spike protein gene) into recipient cells.