Data adopted from references: (Echavarria, 2006; Hierholzer, 1992; Kaneko et al., 2009; Wadell et al., 1980; Walsh et al., 2010; and from National Center for Biotechnology Information database

† according to Ebner et al. (2005) serotype 50 was reclassified into species D and serotype 51 into

The most common source of adenoviral infection after haematopoietic stem cell transplantation is reactivation of a latent virus persisting in lymphocytes of peripheral blood, in adenoids, intestines and kidneys through low-grade replication. AdV1, AdV2 and AdV5 (C) are the most common serotypes remaining latent after primary exposure in the childhood (Lee et al., 2010; Malekshahi et al., 2010). They also play the significant role in development of AdV infections after SCT, therefore confirming the role of virus reactivation during an early post-transplant period. The next source of AdV infection in stem cell recipients might be the virus transmission from the positive donor to the negative recipient.

G 52 ND

whole blood in HSCT recipients usually causing limited infections of the respiratory tract, gastrointestinal system and urinary tract but sometimes progress to disseminated disease affecting many organs and whole systems, too (Watcharananan et al., 2010). The diagnosis of adenoviral infection can be difficult due to complexity of the multiorgan disease nonspecific symptoms resembling other infections or acute graft versus host disease (aGvHD). This review describes adenoviral infections in recipients of hematopoietic stem cell transplantations and focuses attention on infection course, risk factors, possible complications, diagnostic methods for adenovirus identification and therapy strategies.

#### **2. Human adenoviruses-general description**

The original virus was isolated in 1953 from surgically removed adenoids from a child by Rowe et al. (Huebner et al., 1954; Rowe et al., 1953), thus it has been called adenovirus. Adenoviruses are ubiquitous in the environment contaminated with human feces or sewage. To date, 54 antigenic types of human adenoviruses belonging to genus *Mastadenovirus* and family *Adenoviridae* have been described, and over half of them have been recognized as pathogenic for humans. They have been divided into seven species (from A to G) on the basis of their morphological, hemagglutinating and oncogeneic properties as well as their genome size, DNA sequence and electrophoretic mobility of virion polypeptides (Table 1). Adenoviruses from species B and D were further subdivided into subspecies: B1, B2 and D1, D2 and D3, respectively. In addition to this classification several AdV genotypes can be identified within previously mentioned serotypes (Echavarri´a, 2008, 2009; Ebner et al. 2005; Stone et al., 2003; Wadell et al., 1980).

Adenoviruses are non-enveloped, 70-90 nm in diameter particles with icosahedral symmetry. The capsid is composed of 252 capsomers: 240 hexamers and 12 pentons (Russell, 2009; Rux et al., 2003). Several different proteins in AdV particle can be distinguished, but three major proteins such as hexon, penton base and fiber protein create the main capsid structure. The hexon is a homotrimer of three identical polypeptide chains (pII) formulating a triangular vertex of surface loops. It is the most abundant protein in adenoviral particle (more than 80% of AdV2 capsid protein) formulating hexon molecules symmetrically distributed in the capsid (Burnett, 1999). The hexon possess the group− and type−specific determinants which are utilized in diagnostic procedures such as ELISA test, hemagglutination inhibition and serum neutralization. Occurrence of these specific antigen determinants on a viral surface is determined by the presence of variable and hypervariable regions (HVRs) in nucleotide sequence of the hexon gene. Since today, nine hipervariable regions (HVR1-HVR9) have been distinguished (Crawford-Miksza & Schnurr, 1996; Rux et al., 2003). They are situated within the loops at the top of the hexon molecule, hence can be utilized in diagnostic tests. The hexon protein is also an immunodominant T-cell target, however other structural components of the virion may also be immunogenic. Twelve penton bases (pIII) creating capsid vertex provide the basis for radially projecting trimeric fibers (pIV) of different lengths according to the AdV serotype (10-37 nm). The external end of the fiber is terminated with a C-terminal knob which posses several antigen determinants participating in cell receptors binding, hemagglutination in vitro and virus internalization into a host cell (Burmeister et al., 2004; Cusack, 2005; Echavarri´a, 2008). Genetic information of adenoviruses is encoded by about 34-36 kb double stranded linear DNA, containing more than 50 coding regions (Echavarri´a, 2008).

whole blood in HSCT recipients usually causing limited infections of the respiratory tract, gastrointestinal system and urinary tract but sometimes progress to disseminated disease affecting many organs and whole systems, too (Watcharananan et al., 2010). The diagnosis of adenoviral infection can be difficult due to complexity of the multiorgan disease nonspecific symptoms resembling other infections or acute graft versus host disease (aGvHD). This review describes adenoviral infections in recipients of hematopoietic stem cell transplantations and focuses attention on infection course, risk factors, possible complications, diagnostic methods for adenovirus identification and therapy strategies.

The original virus was isolated in 1953 from surgically removed adenoids from a child by Rowe et al. (Huebner et al., 1954; Rowe et al., 1953), thus it has been called adenovirus. Adenoviruses are ubiquitous in the environment contaminated with human feces or sewage. To date, 54 antigenic types of human adenoviruses belonging to genus *Mastadenovirus* and family *Adenoviridae* have been described, and over half of them have been recognized as pathogenic for humans. They have been divided into seven species (from A to G) on the basis of their morphological, hemagglutinating and oncogeneic properties as well as their genome size, DNA sequence and electrophoretic mobility of virion polypeptides (Table 1). Adenoviruses from species B and D were further subdivided into subspecies: B1, B2 and D1, D2 and D3, respectively. In addition to this classification several AdV genotypes can be identified within previously mentioned serotypes (Echavarri´a, 2008, 2009; Ebner et al. 2005;

Adenoviruses are non-enveloped, 70-90 nm in diameter particles with icosahedral symmetry. The capsid is composed of 252 capsomers: 240 hexamers and 12 pentons (Russell, 2009; Rux et al., 2003). Several different proteins in AdV particle can be distinguished, but three major proteins such as hexon, penton base and fiber protein create the main capsid structure. The hexon is a homotrimer of three identical polypeptide chains (pII) formulating a triangular vertex of surface loops. It is the most abundant protein in adenoviral particle (more than 80% of AdV2 capsid protein) formulating hexon molecules symmetrically distributed in the capsid (Burnett, 1999). The hexon possess the group− and type−specific determinants which are utilized in diagnostic procedures such as ELISA test, hemagglutination inhibition and serum neutralization. Occurrence of these specific antigen determinants on a viral surface is determined by the presence of variable and hypervariable regions (HVRs) in nucleotide sequence of the hexon gene. Since today, nine hipervariable regions (HVR1-HVR9) have been distinguished (Crawford-Miksza & Schnurr, 1996; Rux et al., 2003). They are situated within the loops at the top of the hexon molecule, hence can be utilized in diagnostic tests. The hexon protein is also an immunodominant T-cell target, however other structural components of the virion may also be immunogenic. Twelve penton bases (pIII) creating capsid vertex provide the basis for radially projecting trimeric fibers (pIV) of different lengths according to the AdV serotype (10-37 nm). The external end of the fiber is terminated with a C-terminal knob which posses several antigen determinants participating in cell receptors binding, hemagglutination in vitro and virus internalization into a host cell (Burmeister et al., 2004; Cusack, 2005; Echavarri´a, 2008). Genetic information of adenoviruses is encoded by about 34-36 kb double stranded linear DNA, containing more

**2. Human adenoviruses-general description** 

Stone et al., 2003; Wadell et al., 1980).

than 50 coding regions (Echavarri´a, 2008).

