**8. Adenoviral latency**

The term "adenoviruses" has an ecological coloration, reflecting the tendency to persistence in the lymphoid tissue, so that adenoviruses can be isolated from the tonsils, adenoids, appendix, and lymph nodes of practically healthy people.

After acute infections, many serotypes are not eliminated from the body for a long time. Most of the latent viruses belong to subgroups B2 and C. They can persist for years in the lymphoid tissue of the pharyngeal ring and, apparently, other localizations (e.g., in the mesenteric lymph nodes). Once in the intestine, adenoviruses asymptomatically replicate in the epithelial cells and/or Peyer's patches, periodically evolving from feces.

released into the environment through excreta. Therefore, a vaccine containing live strains of adenovirus is not recommended for use in children or the general population. Despite the longterm stability of the adenovirus genome, which is confirmed by the efficacy of ongoing vaccination among the US military, random mutations or homologous recombination events, which can lead to changes in the antigenicity of adenovirus, are not excluded. In addition, over time, the epidemic types of adenovirus have changed, and in recent years, highly pathogenic serotypes 14 and 55 have been distributed throughout the world. Finally, the circulation of the types of adenoviruses can vary geographically; for example, in China, the most common types associated with acute respiratory infections (ARI) are types 3, 7, and 55 [28]. Therefore, attention should be paid to developing new adenoviral vaccines based on currently circulating adenovirus strains.

Introductory Chapter: Human Adenoviruses http://dx.doi.org/10.5772/intechopen.82554 7

Representatives of the genus *Mastadenovirus* served as objects of research in the field of molecular biology. The intrigue around the pathogenetic function of adenoviruses aggravated after their tumorigenic properties, the ability to induce malignant tumors in animals (newborn hamsters), was recorded. In 1962, Trentin et al. described the first case of the induction of a malignant tumor in animals by the human pathogenic virus—adenovirus-12, which caused tumors in rodents [29]. The oncogenic potential of adenoviruses has served as a stimulus for their careful study, which has proved useful for studying the mechanisms of viral infection and molecular processes in eukaryotic cells. On the model of adenovirus infection, splicing, adenylation, and capturing of matrix RNA, sequence and expression regulation of viral genes, their integration with cellular chromosomes, etc. were first studied with human tumors. In a series of works [30, 31], it was shown that high-oncogenic type 12 adenoviruses and type 18 adenoviruses induce chromosomal aberrations in nonpermissive cells for them. The mutagenic effect at the chromosomal level has been demonstrated for human type 2 adenoviruses and type 5 in rat cells [32], as well as for bovine adenovirus type 3 in Chinese hamster cells [33]. In humans, despite intensive research, the association of malignant tumors with adenoviruses has not been identified.

The promise of using adenoviruses as vectors is due to the fact that a relatively large fragment can be inserted into their linear DNA. With the advent of second-generation vectors, it became possible to embed foreign DNA sequences up to 35 kb in the adenovirus genome, while maintaining only inverted repeats and packaging site. In addition, adenovirus receptors (e.g., termination of the fibers) can be genetically modified in such a way as to increase the tropism of the virus in relation to the tumor tissue. As a product of the transgene, which allows to destroy a tumor, you can use the herpes virus thymidine kinase (family *Herpesviridae*) or the chicken anemia virus apoptin (family *Circoviridae*). In the first case, the patient is prescribed of acyclovir; in the second case, the tumor is destroyed as a result of vector-induced apoptosis. Unfortunately, genetically engineered constructions based on adenoviral vectors have not yet found clinical

**12. The use of adenoviruses as vectors for gene therapy**

**11. The mutagenic effect**

Latency creates the possibility of endogenous recurrences of acute infection and chronic hyperplasia (in fact, chronic inflammation) of infected lymphoid tissue. The possibility of activating a viral infection in the tonsils (chronic tonsillitis), mesenteric lymph nodes, and appendix is not excluded. Adenoviruses can be activated on the background of immunosuppressive therapy in AIDS patients. A number of new serotypes (serotypes 43–47 of subgroup D) were first isolated from AIDS patients (from feces), allowing to believe that a persistent infection creates favorable conditions for the evolution of adenoviruses [25].

The mechanism of persistence of adenoviruses in the lymphoid tissue still remains unclear. Most likely, this is due to the low content of sensitive (permissive) cells and very slow replication of the virus in lymphocytes, that is, with severely limited productive infection. It is significant that in the experiments of W. Rowe et al., who discovered adenoviruses in 1953, it took several weeks for the degeneration of a culture of adenoid tissue associated with the reproduction of latent adenoviruses. The possibility of integrative virogeny with partial expression of the viral genome is not excluded. In approximately 50% of the tonsils in adults, it was possible to detect adenoviral antigens in the absence of an infectious virus.
