Introduction

Adenoviruses are naked viruses. Because they have no membrane, they are very stable.  Adenoviruses were first identified in 1953 as agents derived from human adenoid tissues which could induce the spontaneous degeneration of primary cells in culture. There are some 49 human serotypes. They have been classified into six subgroups based upon their ability to agglutinate red blood cells. 

Structure, Transmission and Disease

Adenoviruses are medium-sized (90-100 nm), non-enveloped icosohedral viruses with double-stranded DNA. More than 50 types of immunologically distinct adenoviruses can cause infections in humans. Adenoviruses are relatively resistant to common disinfectants and can be detected on surfaces, such as doorknobs, objects, and water of swimming pools and small lakes.

Adenoviruses are spread by microdroplets and fomites. Pneumonia is a problem in an immunocompromised host. Conjunctivitis is also associated with swimming pool and opthalmic solution (contaminated contact lenses) acquisition of this virus.

Adenoviruses can cause a wide variety of illnesses in humans, from the common cold to gastrointestinal infections to pink eye. 

Adenoviruses most commonly cause respiratory illness. The illnesses can range from the common cold to pneumonia, croup, and bronchitis. Depending on the type, adenoviruses can cause other illnesses such as gastroenteritis, conjunctivitis, cystitis, and, less commonly, neurological disease.  See CDC

Adenoviruses are not deadly pathogens. Rather, though they occasionally cause the common cold and resulting complications, they are a promising tool for the development of new medical technologies and gene therapy techniques. Human adenoviruses are part of the Adenoviridae family, whose representatives also infect animals such as cows, ducks, bats, geckoes, and even sturgeons. In human bodies, adenoviruses attack cells of the upper respiratory tract predominantly, causing flu-like symptoms: runny nose, coughing, pain and inflammation in the nose and throat and — sometimes — conjunctivitis.  See Visual Science

Adenovirus enters cells via clathrin-dependent endocytosis or via micropinocytosis. After partial unpacking in the cytoplasm, the remaining capsid structures carry the genome to the nucleus in a complex with VII-protein. Early genes of adenovirus are united in several groups — transcriptional units. These encode regulatory proteins that activate DNA synthesis in the cell and block the interferon response, thereby preventing the cell from triggering apoptosis. Some of these early transcriptional products also trigger the synthesis of the late structural proteins. 

Adenoviruses are well-equipped to play the role of vectors for the transformation of human cells in medicine. Genes that are needed for viral replication may be easily substituted for by the DNA of interest, and adenovirus particles may be used for its delivery. The simplest variant of this procedure is to delete the adenoviral DNA region that triggers the transcription of most viral proteins (E1A gene), thereby eliminating the virus’s ability to replicate and infect new cells while retaining its ability to express the transgene.  Scientists have used modified adenoviruses to build other vaccines, such as those that protect against COVID-19. These modified viruses can no longer infect human cells, but they instead act as a vehicle for the vaccine to enter the body. See live Science

Spectific Types

Adenovirus 2 (Ad2) was the first adenovirus genome completely sequenced and contains 35,937 bp of DNA. 

1. Characteristics of its genome are the following:

**has inverted terminal repeat sequences which allow the viral DNA to circularize. 

**contains two identical origins of replication which are present in the terminal inverted repeats.

**contains a cis-packaging sequence which allows packaging into the viral particle 

**Ad2 has multiple transcription units and each transcription unit gives rise to multiple RNA species by alternative splicing and poly adenylation. Among its early transcription units are the following:

**E1A: this is an immediate early transcription unit which encodes two proteins E1A 12S and 13S which are transcription factors which stimulate the cells to enter DNA synthesis and which activates expression of other early viral genes. Adenovirus through E1a can induce otherwise quiescent host cells to enter DNA synthesis. This is critical for adenovirus since the genome is not large enough for the virus to encode all the enzymes necessary to synthesize the dNTPs required for DNA synthesis. The first clue as to how E1a could accomplish this task came from the observation that a number of proteins like co-immunoprecipitated with E1a. In normal cells, cyclins stimulate the phosphorylation of Rb which leads to its dissociation from E2F and activation of E2F. This drives the cell into S phase. E1A also disrupts the E2F-Rb complex.

**E1B which encodes two proteins 19 kDa (which can block apoptosis) and 55 KDa (which can target p53) The 55kDa E1B protein interacts with  which is another transcription factor involved in regulating the cell cycle and also .  Specifically, E1B 55 kDA protein binds to p53 and blocks its ability to induce transcription. Thus it blocks p53’s G1 arrest and perhaps more importantly its ability to induce apoptosis. The 19 kDa E1B also blocks apoptosis but at a step down stream of p53. Specifically E1B 19kDA is a BCL2 homolog and blocks apoptosis by dimerizing with and thus mimicking the action of BCL2. 

2. Absorption and Entry of Ad2 starts with (1) attachment of the virus which is mediated by the fiber protein. The receptor is the same as for the coxsackie virus and is called CAR. CAR is not present on all cells, particularly hematopoetic cells, but it is present on many cells which gives adenovrius a wide range of infectivities in tissue culture. (2) Within 10 minutes of absorption the virus-CAR complex is internalized by endocytosis. The complex does not mature into a lysosome. Instead the viral particle blocks maturation and within 5 minutes appears in the cytosol. (3) microtubule-hexon intereactions bring the particle to the nuclear pore (completed by 40 minutes or so). (4) the particle then releases the viral DNA into the nuclus leaving the capside at the pore. (5) the viral DNA associates with the nuclear matrix via intereaction with the TP (this association is essential for transcription of the genome).

Human rotavirus (HRV): is a major etiologic agent of acute infantile gastro-enteritis, infecting up to 90% of children under the age of 3 and is characteristically localized to the epithelial cells of the gastrointestinal tract. The live, oral, rehsus-human rotavirus reassortant-tetravalent vaccine (RRV-TV) was licnsed for use in the US on August 31, 1998. It was subsequently recommended for routine use in infants in a 3 dose series given at 2, 4 and 6 months of age. (Zanardi, Pediatrics 107(6), 2001).  Passive immunization using microencapsulation of  anti-VP8 IgY has been reported as effective by (Kovacs-Nolan, “Microencapsulation for the gastric passage and controlled intestinal release of immunoglobulin Y” J. I.Methods, 296 (2005, 199-209).