Partial block to transcription
of human adenovirus type 2 late genes in abortively infected monkey cells
Characterization of a variant
of human adenovirus type 2 which multiples efficiently in simian cells
Normal translation
of human adenovirus mRNA in cell - free lysates prepared from abortively as well as productively infected monkey cells
Synthesis
of human adenovirus early RNA species is similar in productive and abortive infections of monkey and human cells
Posttranscriptional block to synthesis
of a human adenovirus capsid protein in abortively infected monkey cells
Humans are infected by common serotypes
of human adenovirus such as AdHu5 and a significant percentage has neutralizing antibodies to this serotypes, which impair the efficacy of AdHu5 based vaccines.
These viruses do not circulate in the human population and fail to carry neutralizing B cell epitopes that cross-react with the common serotypes
of human adenoviruses.
Not exact matches
There are innumerable different viruses, but the
human adenovirus 5, which normally causes the symptoms
of a typical cold, has substantial advantages: Its genome can be replaced completely by an artificial one which contains only «useful» genes.
«No data from
humans vaccinated with
adenovirus 5 vectors are described in this paper,» says one
of them, Dan Barouch
of the Beth Israel Deaconess Medical Center at Harvard Medical School.
But in mice that had been exposed to
human adenovirus, only the chimp virus - based vaccine worked, the researchers report in the March issue
of the Journal
of Virology.
A possible problem facing a
human vaccine is that some people already have an immune response to some strains
of adenoviruses, which would reduce the body's response to the vaccine strain.
Now, a new report confirms that the Davis outbreak was the first known case
of an
adenovirus jumping from monkeys to
humans.
To assess cross-neutralization
of TMAdV by known
human adenoviruses, 7 pools
of in - house reference sera at the VRDL (rabbit hyperimmune sera) and collectively containing antibodies to
human adenovirus serotypes 1 through 35 were available for testing.
The discovery
of TMAdV, a novel
adenovirus with the capacity to infect both monkeys and
humans, suggests that
adenoviruses should be monitored closely as potential causes
of cross-species outbreaks.
The significant overall sequence divergence
of TMAdV from known
human and simian
adenoviruses is highlighted by the finding that PAdV - A (porcine
adenovirus A), a non - primate mammalian
adenovirus, shared only a slightly less similar whole - genome pairwise identity to TMAdV
of 47.0 % (Fig. 4).
However, the high sequence divergence in the fiber protein (Table 2), as well as the absence
of fiber motifs conserved among
adenoviruses that bind CAR [36], [37](coxsackievirus -
adenovirus receptor) or CD46 [38], [39], [40](data not shown), suggest that neither
of these two
human adenoviral receptors may be the attachment receptor for TMAdV.
The closest
human adenoviral relatives were the species D
adenoviruses, which share 54.3 % to 55.1 % identity to TMAdV, with
human adenoviruses of other species slightly less similar (51.1 % — 54.6 %).
We used the Virochip, a microarray designed to detect all viruses, to identify a new species
of adenovirus (TMAdV, or titi monkey
adenovirus) that caused a deadly outbreak in a colony
of New World titi monkeys at the California National Primate Research Center (CNPRC), and also infected a
human researcher.
Adenoviruses are DNA viruses that naturally infect many vertebrates, including
humans and monkeys, and cause a wide range
of clinical illnesses in
humans.
After removal
of similar viral genomes, bootscan plots
of the whole genome and individual genes from a subset representing
human / simian
adenoviruses in species A — G and all non-primate vertebrate
adenoviruses were generated.
Human adenoviruses do not usually replicate in monkey cells in the absence
of helper viruses [11], and do not productively infect rodents (and vice versa)[12].
Some serotypes, such as
human adenovirus type 14 (HAdV - 14), have been associated with severe and potentially fatal outbreaks
of pneumonia in residential facilities and military bases [4].
Adenovirus PCR was performed on a TMAdV - positive clinical sample, a TMAdV culture, and a human adenovirus B culture (as a positive control) using an additional 5 pairs of primers, according to previously published protocols [26], [27], [28] Three of the 5 primer pairs, designed to detect human respiratory adenoviruses B, C, and E, failed to amplify T
Adenovirus PCR was performed on a TMAdV - positive clinical sample, a TMAdV culture, and a
human adenovirus B culture (as a positive control) using an additional 5 pairs of primers, according to previously published protocols [26], [27], [28] Three of the 5 primer pairs, designed to detect human respiratory adenoviruses B, C, and E, failed to amplify T
adenovirus B culture (as a positive control) using an additional 5 pairs
of primers, according to previously published protocols [26], [27], [28] Three
of the 5 primer pairs, designed to detect
human respiratory
adenoviruses B, C, and E, failed to amplify TMAdV [27].
Second, our results show that PCR assays for
human adenoviruses in common use are capable
of detecting TMAdV.
In this regard, the high sequence divergence
of TMAdV relative to the known
human / simian
adenoviruses (Fig. 3), and comparable sequence similarity in the polymerase gene to a porcine
adenovirus (Figs. 3 and S1) are striking.
Although sequencing
of PCR amplicons for
human adenoviruses is not performed routinely in diagnostic virology, TMAdV would presumably have been detected previously in large - scale studies
of hexon sequencing
of Ad field isolates if it were circulating in the community [46], [47].
The decreased levels
of neutralizing Abs to TMAdV in the researcher (1 ∶ 32) and a family member (1 ∶ 8) relative to those in infected titi monkeys (up to > 1 ∶ 512) are consistent with a recent study showing much higher levels
of neutralizing antibodies in chimpanzees than in
humans with
adenovirus infections, possibly due to more robust
adenovirus - specific T - cell responses in
humans than in monkeys [45].
Respiratory viral testing failed to detect evidence
of respiratory syncytial virus,
adenovirus, influenza virus A and B,
human metapneumovirus, and parainfluenza virus types 1, 2, and 3.
The scanning nucleotide pairwise identities
of TMAdV relative to representative
human (yellow) or simian (brown)
adenoviruses in species A — G, porcine
adenovirus (red), and fowl
adenovirus (green) are shown.
Open Reading Frame E3 - 10.9 K
of Subspecies B1
Human Adenoviruses Encodes a Family
of Late Orthologous Proteins That Vary in Their Predicted Structural Features and Subcellular Localization.
Such antibodies are expected to reduce the efficacy
of vaccines based on common
human serotypes
of adenovirus in a
human target population.
To do this, a team led by Matthew Weitzman
of the University
of Pennsylvania crosslinked the host factors
of infected
human cells with the DNA
of adenovirus, herpes simplex virus and vaccinia virus.
Characterization
of the translational defect to fiber synthesis in monkey cells abortively infected with
human adenovirus: Role
of ancillary leaders
Scale - Up
of the
Adenovirus Expression System for the Production
of Recombinant Protein in
Human 293S Cells.
Increased permissivity
of monkey cells to
human adenovirus multiplication is affected by culturing conditions and correlates with both synthesis
of virion fiber protein and altered splicing
of its mRNA
Both transient transfection with Lipofectamine and transduction with
adenovirus resulted in a subpopulation
of cells that experessed
human IgG, as shown by the increased fluorescence intensity.
Additional experiments using RNA isolated from stocks
of viruses from different virus families showed no cross reactivity
of the assay with influenza A virus, influenza B virus, rhinovirus,
human coronaviruses 229E, OC43, and NL63, and
adenovirus (data not shown).
It contains highly attenuated strains
of CDV,
human measles virus, canine
adenovirus - 2 (CAV - 2) and canine parainfluenza virus (CPiV).
Improving the oncolytic potency
of agents has been hampered by the inability to study host - vector interactions in immune - competent systems, since
human serotype
adenoviruses do not productively replicate in animal tissues.