Characterization of species B adenoviruses isolated from fecal specimens taken from poliomyelitis-suspected cases

Azevedo, Juliana P.R. de; Nascimento, Luciana R.S.; Cortinovis, Michelle C.S.; Oliveira, Silas S.; Costa, Eliane Veiga da; Silva, Edson E. da

doi:10.1016/j.jcv.2004.04.007

Cited by 14 publications

(12 citation statements)

References 22 publications

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“…HAdV-B3 infection has also been associated with myocarditis (77), which could be explained by the presence of hDSG2 in the intercalated discs of the myocardium. Particularly in immunesuppressed patients, infection with hDSG2-interacting Ads can cause hemorrhagic cystitis (9), pancreatitis (3,36,55), conjunctivitis (51) and also central nervous system (CNS) diseases (15,70). While our DSG2 biodistribution studies provided support for a potential etiological link between HAdV-B infection and these symptoms, it would go beyond this study to explore this further.…”

Section: Hdsg2-transgenic Mice As a Model For The Study Of Ad Infectionmentioning

confidence: 89%

A New Human DSG2-Transgenic Mouse Model for Studying the Tropism and Pathology of Human Adenoviruses

Wang

Beyer

Persson

et al. 2012

J Virol

105

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fWe have recently reported that a group of human adenoviruses (HAdVs) uses desmoglein 2 (DSG2) as a receptor for infection. Among these are the widely distributed serotypes HAdV-B3 and HAdV-B7, as well as a newly emerged strain derived from HAdV-B14. These serotypes do not infect rodent cells and could not up until now be studied in small-animal models. We therefore generated transgenic mice containing the human DSG2 locus. These mice expressed human DSG2 (hDSG2) at a level and in a pattern similar to those found for humans and nonhuman primates. As an initial application of hDSG2-transgenic mice, we used a green fluorescent protein (GFP)-expressing HAdV-B3 vector (Ad3-GFP) and studied GFP transgene expression by quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry subsequent to intranasal and intravenous virus application. After intranasal application, we found efficient transduction of bronchial and alveolar epithelial cells in hDSG2-transgenic mice. Intravenous Ad3-GFP injection into hDSG2-transgenic mice resulted in hDSG2-dependent transduction of epithelial cells in the intestinal and colon mucosa. Our findings give an explanation for clinical symptoms associated with infection by DSG2-interacting HAdVs and provide a rationale for using Ad3-derived vectors in gene therapy. Human adenoviruses (HAdVs) have been classified into six species (HAdV-A to HAdV-F) currently containing 55 serotypes. Most adenovirus (Ad) serotypes utilize the coxsackie-adenovirus receptor (CAR) as a primary attachment receptor. However, this is not the case for species B Ad serotypes. Species B Ads form two genetic clusters, B1 (HAdV-B3, -B7, -B16, -B21, and -B50) and B2 (HAdV-B11p, -B14, -B34, and -B35) (84). Recently, we have suggested a new grouping of species B Ads based on their receptor usage (82). The members of group 1 (HAdV-B16, -B21, -B35, -B50) nearly exclusively utilize CD46 as a receptor; the members of group 2 (HAdV-B3, -B7, -B14) use a receptor that was unknown until recently (receptor X), group 3 (HAdV-B11p) preferentially interacts with CD46 but also utilizes receptor X if CD46 is blocked or absent. This novel receptor usage-based grouping system has been supported by studies from various groups (27,50,65,66). A newly emerged, pathogenic strain, Ad14-p1, uses the same receptor as prototype HAdV-B14 (89).HAdV-B3 and -B7 are considered to be widely distributed human pathogens (14,52,59). Studies from the United States show that HAdV-B3 and -B7 infections occur more often in adolescents and adults (23, 92), while studies from Europe and Asia indicate that these serotypes are also common in children (32,45,90). Since 2005, several outbreaks of HAdV-B14p1 in military facilities and civic communities have been reported in various countries, including the United States, Europe, and Asia (8,48,78). Ads, including HAdV-B3, enter the body via the mouth/nose and generally cause respiratory diseases. The respiratory tract epithelium is also the preferred site of viral replication. Subsequent virusinduced cyto...

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Section: Hdsg2-transgenic Mice As a Model For The Study Of Ad Infectionmentioning

confidence: 89%

A New Human DSG2-Transgenic Mouse Model for Studying the Tropism and Pathology of Human Adenoviruses

Wang

Beyer

Persson

et al. 2012

J Virol

105

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“…We cannot exclude the possibility that other, postentry mechanisms contribute to the differences in tropism that were observed for species B Ads. However, it is tempting to speculate that the affinity for CD46, to a certain extent, contributes to the observed differences in tropism: high affinity (Ad11 and Ad35) correlates with urinary tract tropism, and low affinity (Ad7, Ad14, Ad16, and Ad21) correlates with ocular and/or respiratory tract tropism (10,11,43). Furthermore, Ad8, Ad19, and Ad37, which cause epidemic keratoconjunctivitis, are the only Ads that use sialic acid as a receptor and thus show a clear link to tropism and receptor usage (3).…”

Section: Discussionmentioning

confidence: 99%

“…Species B Ads can be further grouped into subspecies B1 (Ad3, Ad7, Ad16, Ad21, and Ad50) and subspecies B2 (Ad11, Ad14, Ad34, and Ad35). Viruses in the two subspecies differ in their tropisms: while most B1 viruses cause ocular and/or acute respiratory tract infections, the B2 viruses primarily cause persistent infections of the urinary tract as well as eye infections, meningitis, and infections of the gastrointestinal tract (10,11,43). The subspecies B1 Ad21, which is the subject of this study, recently caused outbreaks of acute respiratory disease (28).…”

mentioning

confidence: 99%

Structure of Adenovirus Type 21 Knob in Complex with CD46 Reveals Key Differences in Receptor Contacts among Species B Adenoviruses

Cupelli

Müller

Persson

et al. 2010

J Virol

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The complement regulation protein CD46 is the primary attachment receptor for most species B adenoviruses (Ads). However, significant variability exists in sequence and structure among species B Ads in the CD46-binding regions, correlating with differences in affinity. Here, we report a structure-function analysis of the interaction of the species B Ad21 knob with the two N-terminal repeats SCR1 and SCR2 of CD46, CD46-D2. We have determined the structures of the Ad21 knob in its unliganded form as well as in complex with CD46-D2, and we compare the interactions with those observed for the Ad11 knob-CD46-D2 complex. Surface plasmon resonance measurements demonstrate that the affinity of Ad21 knobs for CD46-D2 is 22-fold lower than that of the Ad11 knob. The superposition of the Ad21 and Ad11 knob structures in complex with CD46-D2 reveals a substantially different binding mode, providing an explanation for the weaker binding affinity of the Ad21 knob for its receptor. A critical difference in both complex structures is that a key interaction point, the DG loop, protrudes more in the Ad21 knob than in the Ad11 knob. Therefore, the protruding DG loop does not allow CD46-D2 to approach the core of the Ad21 knob as closely as in the Ad11 knob-CD46-D2 complex. In addition, the engagement of CD46-D2 induces a conformational change in the DG loop in the Ad21 knob but not in the Ad11 knob. Our results contribute to a more profound understanding of the CD46-binding mechanism of species B Ads and have relevance for the design of more efficient gene delivery vectors.The 52 human adenovirus (Ad) serotypes are divided into seven species (species A to G) (20). Species B Ads are of interest, as they cause severe infections of the respiratory tract, urinary tract, and kidney as well as multiorgan system failure and death in immunocompromised patients (2,23,24). Species B Ads can be further grouped into subspecies B1 (Ad3, Ad7, Ad16, Ad21, and Ad50) and subspecies B2 (Ad11, Ad14, Ad34, and Ad35). Viruses in the two subspecies differ in their tropisms: while most B1 viruses cause ocular and/or acute respiratory tract infections, the B2 viruses primarily cause persistent infections of the urinary tract as well as eye infections, meningitis, and infections of the gastrointestinal tract (10,11,43). The subspecies B1 Ad21, which is the subject of this study, recently caused outbreaks of acute respiratory disease (28).Adenoviruses have a nonenveloped icosahedral capsid with a linear double-stranded DNA (46). The major capsid proteins are the hexon, the penton base, and the fiber. The trimeric fiber protein, which protrudes from each of the 12 capsid vertices, consists of three distinct domains: an N-terminal tail, an elongated shaft, and a globular knob. The knob mediates cellular attachment to the primary receptors CD46 (16,26,38), coxsackievirus and adenovirus receptor (CAR) (36), and sialic acid (3). Virus attachment is followed by internalization into the host cell via clathrin-coated endocytosis and macropinocytosis, triggered by ...

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“…In our study, 12% of the children were infected with more than one entero-or adenovirus type. Since both entero-and adenoviruses can be isolated from stools from healthy asymptomatic carriers and patients with clinical acute flaccid paralysis, their role in to the paralytic illness is not considered proven [de Azevedo et al, 2004;Bahri et al, 2005]. The possible interaction between multiple viruses such as enteroviruses and [Ooi et al, 2003].…”

Section: Discussionmentioning

confidence: 99%

New enteroviruses, EV‐93 and EV‐94, associated with acute flaccid paralysis in the Democratic Republic of the Congo

Junttila

Lévêque

Kabue

et al. 2007

Journal of Medical Virology

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Surveillance of acute flaccid paralysis often identifies enteroviruses not typeable by virus neutralization in cell culture. During 2000 and 2001, 186 isolates from 138 children with acute flaccid paralysis in the Democratic Republic of the Congo were sent for typing to the National Reference Centre for Enteroviruses in Lyon, France. The 5' UTR of the viral genome could be amplified by PCR for 158 isolates from 114 patients. Isolates from 89 patients were neutralizable, and contained non-polio enterovirus types. Seventeen children were infected with more than one entero- or adenovirus; another three were co-infected with both these viruses. Serological typing failed with 19 isolates from 13 (9%) patients. The VP1 region of these strains could be amplified by PCR and sequenced, which revealed that five children were infected with CV-A17, EV-70, EV-76, EV-77, or CV-A13. Two patients were doubly infected, one with CV-A24 and E-9, and another with E-27 and EV-81. Isolates from six children contained strains with divergent VP1 region. The amino acid sequences of these complete VP1 regions diverged >or=28% from published types indicating that they represented two new enterovirus types, tentatively designated EV-93 belonging to HEV-B and EV-94 within HEV-D. The latter enterovirus has in parallel been isolated from sewage in Egypt. In conclusion, there was a high frequency of "untypable" enterovirus isolates from cases with acute flaccid paralysis in the Democratic Republic of the Congo. Six of these were shown to represent two enteroviruses not previously described.

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Characterization of species B adenoviruses isolated from fecal specimens taken from poliomyelitis-suspected cases

Cited by 14 publications

References 22 publications

A New Human DSG2-Transgenic Mouse Model for Studying the Tropism and Pathology of Human Adenoviruses

A New Human DSG2-Transgenic Mouse Model for Studying the Tropism and Pathology of Human Adenoviruses

Structure of Adenovirus Type 21 Knob in Complex with CD46 Reveals Key Differences in Receptor Contacts among Species B Adenoviruses

New enteroviruses, EV‐93 and EV‐94, associated with acute flaccid paralysis in the Democratic Republic of the Congo

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