Characterization of Four New Adenovirus Serotypes Isolated From Chimpanzee Tissue Explants

Basnight, M.; Rogers, Nancy G.; Gibbs, Clarence J.; Gajdusek, D. Carleton

doi:10.1093/oxfordjournals.aje.a121308

Cited by 49 publications

(51 citation statements)

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“…Previous studies regarding this issue provided conflicting views, especially with respect to cross-neutralization between C68 and adenovirus type 4 (3,23,33). In our study, a screen of 50 normal human subjects failed to detect any significant neutralizing antibodies (Ͼ1:10) using the same assay that showed neutralizing antibodies in Ͼ80% of chimpanzees.…”

Section: Discussioncontrasting

confidence: 55%

See 1 more Smart Citation

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Farina

Gao

Xiang

et al. 2001

J Virol

246

250

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An adenovirus previously isolated from a mesenteric lymph node from a chimpanzee was fully sequenced and found to be similar in overall structure to human adenoviruses. The genome of this virus, called C68, is 36,521 bp in length and is most similar to subgroup E of human adenovirus, with 90% identity in most adenovirus type 4 open reading frames that have been sequenced. Substantial differences in the hexon hypervariable regions were noted between C68 and other known adenoviruses, including adenovirus type 4. Neutralizing antibodies to C68 were highly prevalent in sera from a population of chimpanzees, while sera from humans and rhesus monkeys failed to neutralize C68. Furthermore, infection with C68 was not neutralized from sera of mice immunized with human adenovirus serotypes 2, 4, 5, 7, and 12. A replication-defective version of C68 was created by replacing the E1a and E1b genes with a minigene cassette; this vector was efficiently transcomplemented by the E1 region of human adenovirus type 5. C68 vector transduced a number of human and murine cell lines. This nonhuman adenoviral vector is sufficiently similar to human serotypes to allow growth in 293 cells and transduction of cells expressing the coxsackievirus and adenovirus receptor. As it is dissimilar in regions such as the hexon hypervariable domains, C68 vector avoids significant cross-neutralization by sera directed against human serotypes.Vectors based on human adenovirus subgroup C (i.e., types 2 and 5) have realized widespread application in preclinical and clinical models of gene therapy (34). The viruses are rendered replication defective by deletion of E1 sequences. Multiple essential genes are disabled in more advanced versions of adenovirus vectors (7,10,17,31). An important limitation of the use of adenovirus type 2-and adenovirus type 5-based vectors for human applications is that many individuals are immune to the virus as the result of a previous natural infection (6). A manifestation of existing immunity to the virus is B-cell activation, leading to persistent neutralizing antibodies that block vector uptake in vivo and diminish transduction.One approach to accomplish immunologic distinction is to engineer the capsid of an adenovirus type 5-or adenovirus type 2-based vector. Several studies have attempted to accomplish this by exchanging the gene encoding fiber, since the protein is directly involved in receptor binding. While this has been successful in redirecting uptake of vector via a pathway distinct from that directed by the coxsackievirus and adenovirus (CAR) receptor, such chimeric viruses are still cross-neutralized due to blocking antibodies directed against hexon epitopes in the hypervariable regions (11,14,19,28,31). Recent attempts to engineer hexon proteins in chimeric viruses have been complicated by serotype-specific constraints in the hexon structure, which compromise the formation of stable chimeras. Selective modification of the hypervariable regions of hexon have diminished type-specific cross-neutralization in vitro...

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Section: Discussioncontrasting

confidence: 55%

“…The adenovirus, called C68, was originally isolated from a mesenteric lymph node of a chimpanzee and shown to replicate in a number of primatederived cell lines (3). Detailed restriction endonuclease mapping demonstrated similarities of C68 to human adenovirus serotype 4 (subgroup E) (21,32).…”

mentioning

confidence: 99%

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Farina

Gao

Xiang

et al. 2001

J Virol

246

250

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“…Viruses were isolated from fecal samples, propagated in cell culture, completely sequenced, and tentatively named SAdV-25.2 to SAdV-50 (46). Most SAdVs were found to be very similar to HAdVs and grouped correspondingly into the HAdV-B, -C, -E, and -G groups (see Table S1 in the supplemental material) (4,6,33,34,36,45,46,56). More distantly related simian AdVs were assigned to SAdV-A (8,33).…”

Section: Human Adenovirus B Human Adenovirus C Human Adenovirus D mentioning

confidence: 99%

“…Most of the SAdVs known to date were detected in or isolated from captive individuals and propagated in cell culture (3,4,6,31,33,34,36,45,46,56). Unfortunately, little is known about SAdVs in wild animals.…”

Section: Human Adenovirus B Human Adenovirus C Human Adenovirus D mentioning

confidence: 99%

Novel Adenoviruses in Wild Primates: a High Level of Genetic Diversity and Evidence of Zoonotic Transmissions

Wevers

Metzger

Babweteera³

et al. 2011

J Virol

102

100

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Adenoviruses (AdVs) broadly infect vertebrate hosts, including a variety of nonhuman primates (NHPs).In the present study, we identified AdVs in NHPs living in their natural habitats, and through the combination of phylogenetic analyses and information on the habitats and epidemiological settings, we detected possible horizontal transmission events between NHPs and humans. Wild NHPs were analyzed with a pan-primate AdV-specific PCR using a degenerate nested primer set that targets the highly conserved adenovirus DNA polymerase gene.

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“…Because AdHu5 virus is a ubiquitous human pathogen and ϳ45% of the adult human population in the United States carries virus-neutralizing Abs to AdHu5 virus (12), we developed an alternative E1-deleted adenoviral vaccine carrier derived from an adenovirus that had been isolated from a chimpanzee (13). This virus, termed AdC68, does not circulate in humans nor do Abs to common human serotypes of adenovirus neutralize it (12).…”

mentioning

confidence: 99%

Mucosally Delivered E1-Deleted Adenoviral Vaccine Carriers Induce Transgene Product-Specific Antibody Responses in Neonatal Mice

Xiang

Gao

et al. 2003

The Journal of Immunology

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E1-deleted adenoviral vectors of the human serotype 5 (AdHu5) and the chimpanzee serotype 68 (AdC68) expressing the rabies virus glycoprotein (rab.gp) were tested for induction of transgene product-specific Abs upon intranasal or oral immunization of newborn mice. Both vectors induced Abs to rabies virus that could be detected in serum and from mucosal secretions. Serum rabies virus neutralizing Ab titers sufficed to protect neonatally vaccinated mice against a subsequent challenge with rabies virus. The efficacy of the AdHu5rab.gp vector given orally to newborn mice born to AdHu5 virus-immune dams was not impaired by maternally transferred Abs to the vaccine carrier.

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Characterization of Four New Adenovirus Serotypes Isolated From Chimpanzee Tissue Explants

Cited by 49 publications

References 0 publications

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Novel Adenoviruses in Wild Primates: a High Level of Genetic Diversity and Evidence of Zoonotic Transmissions

Mucosally Delivered E1-Deleted Adenoviral Vaccine Carriers Induce Transgene Product-Specific Antibody Responses in Neonatal Mice

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