Xavier Allaume - Academia.edu (original) (raw)

Papers by Xavier Allaume

Research paper thumbnail of Changing the targeting of rat parvovirus H-1PV against cancer cells by genetic engineering of the capsid

Research paper thumbnail of Novel Human Erythrovirus Associated with Transient Aplastic Anemia

Journal of Clinical Microbiology, 1999

Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemi... more Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemia due to aplastic crisis. Diagnosis of B19 infection relies on serology and the detection of viral DNA by PCR. These techniques are usually thought to detect all erythrovirus field isolates, since the B19 genome is known to undergo few genetic variations. We have detected an erythrovirus (V9) markedly different from B19 in the serum and bone marrow of a child with transient aplastic anemia. The B19 PCR assay yielded a product that hybridized only very weakly to the B19-specific probe and whose sequence diverged more from those of 24 B19 viruses (11 to 14%) than the divergence found within the B19 group (≤6.65%). Restriction enzyme analysis of the V9 genome revealed that this genetic divergence extended beyond the amplified region. Interestingly, serological tests failed to demonstrate a response characteristic of acute B19 infection. V9 could be a new erythrovirus, and new diagnostic tes...

Research paper thumbnail of Through Its Nonstructural Protein NS1, Parvovirus H-1 Induces Apoptosis via Accumulation of Reactive Oxygen Species

Journal of Virology, 2010

The rat parvovirus H-1 (H-1PV) attracts high attention as an anticancer agent, because it is not ... more The rat parvovirus H-1 (H-1PV) attracts high attention as an anticancer agent, because it is not pathogenic for humans and has oncotropic and oncosuppressive properties. The viral nonstructural NS1 protein is thought to mediate H-1PV cytotoxicity, but its exact contribution to this process remains undefined. In this study, we analyzed the effects of the H-1PV NS1 protein on human cell proliferation and cell viability. We show that NS1 expression is sufficient to induce the accumulation of cells in G 2 phase, apoptosis via caspase 9 and 3 activation, and cell lysis. Similarly, cells infected with wild-type H-1PV arrest in G 2 phase and undergo apoptosis. Furthermore, we also show that both expression of NS1 and H-1PV infection lead to higher levels of intracellular reactive oxygen species (ROS), associated with DNA double-strand breaks. Antioxidant treatment reduces ROS levels and strongly decreases NS1- and virus-induced DNA damage, cell cycle arrest, and apoptosis, indicating that ...

Research paper thumbnail of 692 Genetic Engineering of Oncolytic H-1 Parvovirus Capsid Increases Virus Specificity for Cancer Cells

European Journal of Cancer, 2012

Intraepithelial Lesion, HGSIL-High-Grade Intraepithelial Lesion and SCC-Squamous Cell Carcinoma) ... more Intraepithelial Lesion, HGSIL-High-Grade Intraepithelial Lesion and SCC-Squamous Cell Carcinoma) and tested for HPV DNA presence (Linear Array HPV Genotyping Test, Roche Diagnostics). TaqMan SNP Genotyping Assays (Applied Biosystems) were used for SNP detection. Results: Our study showed that in women with normal cytology and ASCUS, hrHPV was absent. On the other hand, 72.2% (13/18) LGSIL and 93.3% (14/15) HGSIL patients presented infection with hrHPV in single or co-infection represented mainly by HPV16, 18, 31 and 33. We detected a significantly greater incidence of mtDNA polymorphisms T239C, A263G and C150T and a lower incidence of T16189C, C16223T in patients cervical lesions compared to controls. We determined that the C150T and T239C polymorphisms were strongly corelated with high risk HPV-positive LGSIL and HGSIL lesions (P < 0.05). Furthermore, HPV-positive individuals were more likely to carry the C150T, A263G and T16189C polymorphisms than HPV-negative controls (P < 0.003). A positive corelation between HPV-positive HGSIL patients and A263G SNP was found in our study group. In all SCC subjects, an increased risk of HPV infection was also associated with the selected polymorphisms (P < 0.02). Conclusion: These findings suggest that mitochondrial SNPs in the D-loop region may represent a cofactor in HPV-induced cervical lesions and cancer but their role in the mechanism of carcinogenesis remains to be solved.

Research paper thumbnail of Retargeting of Rat Parvovirus H-1PV to Cancer Cells through Genetic Engineering of the Viral Capsid

Journal of Virology, 2012

The rat parvovirus H-1PV is a promising anticancer agent given its oncosuppressive properties and... more The rat parvovirus H-1PV is a promising anticancer agent given its oncosuppressive properties and the absence of known side effects in humans. H-1PV replicates preferentially in transformed cells, but the virus can enter both normal and cancer cells. Uptake by normal cells sequesters a significant portion of the administered viral dose away from the tumor target. Hence, targeting H-1PV entry specifically to tumor cells is important to increase the efficacy of parvovirus-based treatments. In this study, we first found that sialic acid plays a key role in H-1PV entry. We then genetically engineered the H-1PV capsid to improve its affinity for human tumor cells. By analogy with the resolved crystal structure of the closely related parvovirus minute virus of mice, we developed an in silico three-dimensional (3D) model of the H-1PV wild-type capsid. Based on this model, we identified putative amino acids involved in cell membrane recognition and virus entry at the level of the 2-fold axi...

Research paper thumbnail of Changing the targeting of rat parvovirus H-1PV against cancer cells by genetic engineering of the capsid

Research paper thumbnail of Novel Human Erythrovirus Associated with Transient Aplastic Anemia

Journal of Clinical Microbiology, 1999

Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemi... more Erythrovirus (formerly parvovirus) B19 causes a wide range of diseases in humans, including anemia due to aplastic crisis. Diagnosis of B19 infection relies on serology and the detection of viral DNA by PCR. These techniques are usually thought to detect all erythrovirus field isolates, since the B19 genome is known to undergo few genetic variations. We have detected an erythrovirus (V9) markedly different from B19 in the serum and bone marrow of a child with transient aplastic anemia. The B19 PCR assay yielded a product that hybridized only very weakly to the B19-specific probe and whose sequence diverged more from those of 24 B19 viruses (11 to 14%) than the divergence found within the B19 group (≤6.65%). Restriction enzyme analysis of the V9 genome revealed that this genetic divergence extended beyond the amplified region. Interestingly, serological tests failed to demonstrate a response characteristic of acute B19 infection. V9 could be a new erythrovirus, and new diagnostic tes...

Research paper thumbnail of Through Its Nonstructural Protein NS1, Parvovirus H-1 Induces Apoptosis via Accumulation of Reactive Oxygen Species

Journal of Virology, 2010

The rat parvovirus H-1 (H-1PV) attracts high attention as an anticancer agent, because it is not ... more The rat parvovirus H-1 (H-1PV) attracts high attention as an anticancer agent, because it is not pathogenic for humans and has oncotropic and oncosuppressive properties. The viral nonstructural NS1 protein is thought to mediate H-1PV cytotoxicity, but its exact contribution to this process remains undefined. In this study, we analyzed the effects of the H-1PV NS1 protein on human cell proliferation and cell viability. We show that NS1 expression is sufficient to induce the accumulation of cells in G 2 phase, apoptosis via caspase 9 and 3 activation, and cell lysis. Similarly, cells infected with wild-type H-1PV arrest in G 2 phase and undergo apoptosis. Furthermore, we also show that both expression of NS1 and H-1PV infection lead to higher levels of intracellular reactive oxygen species (ROS), associated with DNA double-strand breaks. Antioxidant treatment reduces ROS levels and strongly decreases NS1- and virus-induced DNA damage, cell cycle arrest, and apoptosis, indicating that ...

Research paper thumbnail of 692 Genetic Engineering of Oncolytic H-1 Parvovirus Capsid Increases Virus Specificity for Cancer Cells

European Journal of Cancer, 2012

Intraepithelial Lesion, HGSIL-High-Grade Intraepithelial Lesion and SCC-Squamous Cell Carcinoma) ... more Intraepithelial Lesion, HGSIL-High-Grade Intraepithelial Lesion and SCC-Squamous Cell Carcinoma) and tested for HPV DNA presence (Linear Array HPV Genotyping Test, Roche Diagnostics). TaqMan SNP Genotyping Assays (Applied Biosystems) were used for SNP detection. Results: Our study showed that in women with normal cytology and ASCUS, hrHPV was absent. On the other hand, 72.2% (13/18) LGSIL and 93.3% (14/15) HGSIL patients presented infection with hrHPV in single or co-infection represented mainly by HPV16, 18, 31 and 33. We detected a significantly greater incidence of mtDNA polymorphisms T239C, A263G and C150T and a lower incidence of T16189C, C16223T in patients cervical lesions compared to controls. We determined that the C150T and T239C polymorphisms were strongly corelated with high risk HPV-positive LGSIL and HGSIL lesions (P < 0.05). Furthermore, HPV-positive individuals were more likely to carry the C150T, A263G and T16189C polymorphisms than HPV-negative controls (P < 0.003). A positive corelation between HPV-positive HGSIL patients and A263G SNP was found in our study group. In all SCC subjects, an increased risk of HPV infection was also associated with the selected polymorphisms (P < 0.02). Conclusion: These findings suggest that mitochondrial SNPs in the D-loop region may represent a cofactor in HPV-induced cervical lesions and cancer but their role in the mechanism of carcinogenesis remains to be solved.

Research paper thumbnail of Retargeting of Rat Parvovirus H-1PV to Cancer Cells through Genetic Engineering of the Viral Capsid

Journal of Virology, 2012

The rat parvovirus H-1PV is a promising anticancer agent given its oncosuppressive properties and... more The rat parvovirus H-1PV is a promising anticancer agent given its oncosuppressive properties and the absence of known side effects in humans. H-1PV replicates preferentially in transformed cells, but the virus can enter both normal and cancer cells. Uptake by normal cells sequesters a significant portion of the administered viral dose away from the tumor target. Hence, targeting H-1PV entry specifically to tumor cells is important to increase the efficacy of parvovirus-based treatments. In this study, we first found that sialic acid plays a key role in H-1PV entry. We then genetically engineered the H-1PV capsid to improve its affinity for human tumor cells. By analogy with the resolved crystal structure of the closely related parvovirus minute virus of mice, we developed an in silico three-dimensional (3D) model of the H-1PV wild-type capsid. Based on this model, we identified putative amino acids involved in cell membrane recognition and virus entry at the level of the 2-fold axi...