The degree of genetic variability among adenovirus type 4 strains isolated from man and chimpanzee

Li, Quan-Gen; Wadell, Göran

doi:10.1007/bf01314652

Cited by 50 publications

(65 citation statements)

References 27 publications

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“…Chimpanzee adenovirus C68 was obtained from the ATCC and propagated in human 293 cells. Viral genomic DNA was isolated from purified virions using established procedures (9) and digested with a panel of restriction enzymes; the data were consistent with previous studies (data not shown) (21,23,32). Restriction fragments spanning the entire genome of C68 were subcloned into plasmids.…”

Section: Resultssupporting

confidence: 57%

“…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: 56%

See 1 more Smart Citation

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Farina

Gao

Xiang

et al. 2001

J Virol

245

242

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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: Resultssupporting

confidence: 57%

Section: Discussioncontrasting

confidence: 56%

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Farina

Gao

Xiang

et al. 2001

J Virol

245

242

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“…All samples showed identical patterns with all 3 enzymes and were identified as corresponding to genome serotype 4a, as described by Li and Wadell [23].…”

Section: Participantssupporting

confidence: 58%

“…Serotyping of adenovirus isolates was performed using molecular techniques described and validated elsewhere [21]. Adenovirus isolates were further characterized by restriction-enzyme analysis of viral DNA with the endonucleases BamHI, DraI, and SmaI, as described elsewhere [22], and genome type identification and denomination was performed as described by Li and Wadell [23].…”

Section: Laboratory Processingmentioning

confidence: 99%

Transmission Dynamics and Prospective Environmental Sampling of Adenovirus In a Military Recruit Setting

Russell¹,

Broderick²,

Franklin³

et al. 2005

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Background. High levels of morbidity caused by adenovirus among US military recruits have returned since the loss of adenovirus vaccines in 1999. The transmission dynamics of adenovirus have never been well understood, which complicates prevention efforts.Methods. Enrollment and end-of-study samples were obtained and active surveillance for febrile respiratory illnesses (FRIs) was performed for 341 recruits and support personnel. Environmental samples were collected simultaneously. Classic and advanced diagnostic techniques were used.Results. Seventy-nine percent (213/271) of new recruits were seronegative for either adenovirus serotype 4 (Ad-4) or adenovirus serotype 7 (Ad-7). FRI caused by Ad-4 was observed in 25% (67/271) of enrolled recruits, with 100% of them occurring in individuals with enrollment titers !1:4. The percentage of recruits seropositive for Ad-4 increased from 34% at enrollment to 97% by the end of the study. Adenovirus was most commonly detected in the environment on pillows, lockers, and rifles.Conclusions. Potential sources of adenovirus transmission among US military recruits included the presence of adenovirus on surfaces in living quarters and extended pharyngeal viral shedding over the course of several days. The introduction of new recruits, who were still shedding adenovirus, into new training groups was documented. Serological screening could identify susceptible recruits for the optimal use of available vaccines. New high-throughput technologies show promise in providing valuable data for clinical and research applications.

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“…In Japan, no AdV-4 strains were isolated from patients with adenoviral conjunctivitis from 1974 through 1977, but in 1979 and 1980, 33 AdV-4s were isolated from patients with conjunctivitis (2). By DNA restriction analysis, Wadell et al showed that there were at least two genome types of AdV-4, the AdV-4 prototype (AdV-4p) and AdV-4a, and made it clear that since 1965, AdV-4a has caused many outbreaks of adenoviral conjunctivitis throughout the world, including China, the United States, and Holland (13,29). In Japan, AdV-4a also became the major cause of adenoviral conjunctivitis from 1980.…”

mentioning

confidence: 99%

New Genome Type of Adenovirus Serotype 4 Caused Nosocomial Infections Associated with Epidemic Conjunctivitis in Japan

et al. 2004

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Human adenovirus type 4 is one of the major serotypes isolated from patients with adenoviral conjunctivitis. In 2001 we encountered nosocomial infections with epidemic conjunctivitis in the ophthalmology ward of one hospital in Sapporo, which is in the northern part of Japan. Adenoviruses were isolated from the patients with this nosocomial infection and identified as adenovirus type 4 (AdV-4) by a neutralization test with serotypespecific antiserum. When the cleavage patterns of the isolates were compared with the full viral genome with BamHI and SmaI, the cleavage patterns of the isolates were shown to be different from those of AdV-4p and other previously known AdV-4 variants. The nucleotide sequences of the fiber gene of the isolates showed the highest homologies (94.3%) with AdV-4 among the nucleotide sequences available from GenBank and formed a monophyletic cluster along with the prototype strain of AdV-4. The isolates, however, were located in a different lineage from those of AdV-4p and the AdV-4 variant from the sporadic infections. We conclude that the nosocomial infection that appeared in 2001 was caused by a new genome type of AdV-4, which was designated AdV-4c.

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The degree of genetic variability among adenovirus type 4 strains isolated from man and chimpanzee

Cited by 50 publications

References 27 publications

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Replication-Defective Vector Based on a Chimpanzee Adenovirus

Transmission Dynamics and Prospective Environmental Sampling of Adenovirus In a Military Recruit Setting

New Genome Type of Adenovirus Serotype 4 Caused Nosocomial Infections Associated with Epidemic Conjunctivitis in Japan

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