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Ling, Paul ( Baylor College of Medicine )
Zhang, Shaojie ( Baylor College of Medicine )
We focused on reactivation and shedding of human herpesvirus EBV and human polyomaviruses, agents known to establish persistent infections and to undergo reactivation and cause disease, including cancer, when the host immune system is compromised. Animal models were used to study radiation effects on viral infections and host responses to those infections.
The specific aims of the project were: (1) To determine the effects of space radiation and hind limb unloading (HLU) on host control of virus infections and virus-induced cancers in a mouse model; and (2) To characterize direct effects of radiation on viruses and virus-infected cells.
Key findings of the project were from the mouse polyoma virus space radiation model we developed. A quantitative real-time polymerase chain reaction (RQ-PCR) assay was developed to measure murine polyoma virus (MuPyV) genome copies in infected animal tissues. This model showed that gamma-irradiation leads to immunosuppression, delayed clearance of primary virus infection, and reactivated latent viral infections. Both single high-dose and multiple low doses of gamma-irradiation cause virus reactivation. HLU, which simulates aspects of weightlessness, was applied to the mouse model. HLU results in loss of control of virus infection in a tissue-specific manner. Another finding was the identification of a herpesvirus EBV latent protein that might modulate the development of EBV-associated disease. In collaboration with Dr. G. Sonnenfeld we carried out measurements of virus reactivations in volunteers participating in the NASA-sponsored Bed Rest Study, a model for the effects of space flight conditions on human physiology.
Bioastronautics Investigators' Workshop, Poster #90, 2005. , Jan-2005
Bioastronautics Investigators' Workshop, Poster #91, 2005. , Jan-2005
Ling, Paul ( Baylor College of Medicine )
Zhang, Shaojie ( Baylor College of Medicine )
The general hypothesis being addressed is that conditions of long-duration space flight, including radiation, stress, isolation, containment, and sleep deprivation will alter human immune responses, leading to reactivation of latent viruses, increased viral infections and viral disease, and possible development of malignancies. We are focusing on reactivation and shedding of human herpesvirus EBV and human polyomaviruses, agents known to establish persistent infections and to undergo reactivation and cause disease, including cancer, when the host immune system is compromised. Animal models are being used to study radiation effects on viral infections and host responses to those infections.
The specific aims of the project are: (1) To determine the effects of space radiation and hind limb unloading (HLU) on host control of virus infections and virus-induced cancers; and (2) To characterize direct effects of radiation on viruses and virus-infected cells.
Key findings of the project this year were from the mouse polyoma virus space radiation model we developed. This model showed that gamma-irradiation leads to immunosuppression, delayed clearance of primary virus infection, and reactivated latent viral infections. Both single high-dose and multiple low doses of gamma-irradiation cause virus reactivation. HLU, that simulates aspects of weightlessness, was applied to the mouse model. HLU results in loss of control of virus infection in a tissue-specific manner. Combined effects of HLU and virus infection resulted in increased mortality.
Plans for the coming year include experiments to further examine the effect of multiple, low-dose radiation exposures on host control of viral infections; expanded analysis of the effects of HLU and irradiation on control of polyoma virus infection, reactivation, and immune impairment; determination of cytokine and chemokine mRNA levels in tissues from HLU studies; measurements of virus reactivations in volunteers participating in the NASA-sponsored Bed Rest Study, a model for the effects of space flight conditions on human physiology, in collaboration with Dr. G. Sonnenfeld; and studies of radiation-induced signals that cause EBV reactivation from latency in cultured cells.
Ling, Paul ( Baylor College of Medicine )
Zhang, Shaojie ( Baylor College of Medicine )


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