The type species of the genus Megalocytivirus (Infectious spleen and kidney necrosis virus; ISKNV) exhibits low host specificity, with strains infecting >150 species of freshwater, brackish, and marine fishes [7,30]. The recent characterization of the TSIV from Canadian threespine stickleback (Gasterosteus aculeatus) [20] and SDDV from Asian seabass (Lates calcarifer) [21] have revealed the existence of genetically-divergent megalocytiviruses that have been argued to represent new species. The discovery of iridoviruses distantly related to ISKNV has stimulated discussion by members of the International Committee on Taxonomy of Viruses study group on iridoviruses to begin re-evaluating the criteria used in defining megalocytivirus species [13]. The genome annotation of ECIV revealed that it possesses 108 predicted genes (including eight unique genes), and compared to other fully-sequenced megalocytivirus genomes, ECIV has the longest genome and a low %GC content similar to SDDV. These data, taken together with the genetic and phylogenetic analyses, suggest ECIV represents yet another novel megalocytivirus, and we propose the formal species designation of European chub iridovirus to be considered for approval by the International Committee on Taxonomy of Viruses.
The HIRAN domain-containing protein (ECIV ORF 49) is not observed in other viruses, except in some bacteriophages [31], and displayed the highest amino acid (AA) sequence identity (39.1%) to the protein of a zygomycete fungus (Basidiobolus meristosporus). The HIRAN domain has been found as a standalone protein in a wide range of bacteria or fused to other catalytic domains in eukaryotes [31]. The HIRAN domain is predicted to function as a DNA-binding domain that recognizes damaged DNA or stalled replication forks and recruits repair and remodeling enzymes to these sites [31]. Although a variety of DNA viruses encode serpin proteins, lymphocystis disease virus Sa isolate SA9 (ORF 50R; GenBank accession number "type":"entrez-nucleotide","attrs":"text":"KX643370","term_id":"1052158087","term_text":"KX643370"KX643370), SDDV (ORFs 45R and 97L; GenBank accession number "type":"entrez-nucleotide","attrs":"text":"KR139659","term_id":"910268962","term_text":"KR139659"KR139659), and ECIV (ORFs 31 and 57) are the only iridoviruses that possess these genes [32]. Recent studies have demonstrated that poxvirus-encoded serpins subvert host immune responses by inhibiting the inflammatory response and apoptosis [33]. Megalocytiviruses are the only member of the family Iridoviridae to encode ANK repeat proteins, and ECIV encodes the greatest number of copies (ORFs 2, 5, 18, 58, 65, 82, and 89) among members of the genus. ANK repeat proteins have also been described in poxviruses, mimiviruses, and phycodnaviruses. The ISKNV ANK repeat protein (ISKNV ORF 124L; GenBank accession number "type":"entrez-nucleotide","attrs":"text":"AF371960","term_id":"19773610","term_text":"AF371960"AF371960) has been shown to interfere with TNF-α-induced NF-κB activation, an important immune regulatory pathway [34]. Poxvirus-encoded ANK repeat proteins are suggested to be involved with host cell tropism [35] and manipulation of the host cell ubiquitin-proteasome machinery [36]. The US22 proteins are present in all megalocytiviruses, except in SDDV and ISKNV, and these proteins are believed to counter diverse host immune responses by interacting with specific host proteins [37,38]. The highest AA sequence identity of the ECIV US22 protein (ORF 97) to Asian swamp eel suggests it was acquired from a fish host.
The in vitro cultivation of megalocytiviruses is challenging, with propagation reported in a handful of cell lines including the grunt fin cell line for RSIV and three spot gourami iridovirus [17,30], the mandarin fish fry cell line for ISKNV [39], and the turbot fin cell line for TRBIV [40]. Commonly-used cell lines failed in the propagation of the Banggai cardinalfish iridovirus, a strain of the ISKNV genotype, including the epithelioma papulosum cyprini (EPC), bluegill fry (BF-2), chinook salmon embryo (CHSE-214), and fathead minnow (FHM) cell lines [41]. Similarly, TSIV was refractory to culture on EPC, BF-2, and CHSE-214 cell lines [20]. In contrast, ECIV is less fastidious than other megalocytiviruses growing on EPC, BF-2, CHSE-214, KF-1, and CCB cell lines. Whether the related SDDV shares similar in vitro growth characteristics with ECIV remains to be determined as SDDV has only been tested and cultivated in the seabass kidney cell line [21].
Solid organ transplant recipients (SOTRs) are at high risk of viral opportunistic infections, especially during the first six months posttransplant. Human cytomegalovirus (HCMV) remains one of the most important pathogens in transplant recipients, despite the great efforts in diagnosis and effective antiviral therapies. Immunological monitoring could be useful in order to guarantee a better management of the patients. In this setting, several methods have been employed. The review summarizes the most important approaches in immunological monitoring of HCMV-specific T-cell response in transplant setting.
Solid organ transplant recipients (SOTRs) are at high risk of viral opportunistic infections, especially during the first six months post-transplant, due to the immunosuppressive treatments. Human cytomegalovirus (HCMV) remains one of the most important pathogens in transplant recipients, despite the great efforts in diagnosis and effective antiviral therapies [1]. HCMV infections are thought to be responsible of both "direct effect" in the allograft, including inflammation, vasculopathy and fibrosis, and "indirect effect", that are mainly immune-mediated [2]. Great efforts have been devoted in order to implement advanced diagnostic techniques for monitoring HCMV infections in transplant recipients [3-5]. Furthermore, in recent years, the introduction of antiviral prophylaxis and pre-emptive strategies reduced HCMV-related mortality and morbidity [6].
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