13 research outputs found
The Canine Papillomavirus and Gamma HPV E7 Proteins Use an Alternative Domain to Bind and Destabilize the Retinoblastoma Protein
The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can independently transform fibroblasts in vitro, primarily due to its ability to associate with and degrade the retinoblastoma tumor suppressor protein, pRb. The binding of E7 to pRb is mediated by a conserved Leu-X-Cys-X-Glu (LXCXE) motif in the conserved region 2 (CR2) of E7 and this domain is both necessary and sufficient for E7/pRb association. In the current study, we report that the E7 protein of the malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in E7 abrogates pRb binding and degradation. However, despite variation at this critical site, the canine papillomavirus E7 protein still bound and degraded pRb. Even complete deletion of the LXSXE domain of canine E7 failed to interfere with binding to pRb in vitro and in vivo. Rather, the dominant binding site for pRb mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2 domains of HPV E7 are sufficient for degradation of pRb, the C-terminal region of canine E7 was also required for pRb degradation. Screening of HPV genome sequences revealed that the LXSXE motif of the canine E7 protein was also present in the gamma HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds pRb in a similar way. It appears, therefore, that the type 2 canine PV and gamma-type HPVs not only share similar properties with respect to tissue specificity and association with immunosuppression, but also the mechanism by which their E7 proteins interact with pRb
Geostatistical analysis of the spatial distribution of mycotoxin concentration in bulk cereals
Deoxynivalenol (DON) and ochratoxin A (OTA) in agricultural commodities present
hazards to human and animal health. Bulk lots are routinely sampled for their
presence, but it is widely acknowledged that designing sampling plans is
particularly problematical because of the heterogeneous distribution of the
mycotoxins. Previous studies have not take samples from bulk. Sampling plans are
therefore designed on the assumption of random distributions. The objective of
this study was to analyse the spatial distribution of DON and OTA in bulk
commodities with geostatistics. This study was the first application of
geostatistical analysis to data on mycotoxins contamination of bulk commodities.
Data sets for DON and OTA in bulk storage were collected from the literature and
personal communications, of which only one contained data suitable for
geostatistical analysis. This data set represented a 26-tonne truck of wheat
with a total of 100 sampled points. The mean concentrations of DON and OTA were
1342 and 0.59 mu g kg(-1), respectively. The results showed that DON presented
spatial structure, whilst OTA was randomly distributed in space. This difference
between DON and OTA probably reflected the fact that DON is produced in the
field, whereas OTA is produced in storage. The presence of spatial structure for
DON implies that sampling plans need to consider the location of sample points
in addition to the number of points sampled in order to obtain reliable
estimates of quantities such as the mean contamination
Human Papillomaviruses and the Interferon Response
Human papillomaviruses (HPV) are small DNA viruses that target stratified keratinocytes for infection. A subset of HPV types infect epithelia in the genital tract and are the causative agents of cervical as well as other anogenital cancers. Interferon treatment of existing genital HPV lesions has had mixed results. While HPV proteins down-regulate the expression of interferon-inducible genes, interferon treatment ultimately induces their high-level transcription after a delay. Cells containing complete HPV genomes that are able to undergo productive replication upon differentiation are sensitive to interferon-induced growth arrest, while cells from high-grade cancers that only express E6 and E7 are resistant. Recent studies indicate this sensitivity is dependent upon the binding of the interferon-inducible factor, p56, to the E1 replication protein. The response to interferon by HPV proteins is complex and results from the action of multiple viral proteins