Abstract
The human polyomavirus JC PyV lytic infection of oligodendrocytes in the human brain results in the demyelinating disease progressive multifocal leukoencephalopathy, PML. JCV is a common virus infection in the population that leads to PML in patients with underlying diseases and therapies that cause immune deficiencies or modulate immune system functions. Patients may have high levels of antibody to JCV that neither protect them from PML nor clear the infection once PML is established. Cell-mediated immunity plays a more effective role in clearing initial or reactivated JCV infection before PML occurs. However, patients with underlying diseases and therapies for treatment are at high risk for PML. MS patients on natalizumab are one of the categories with the highest incidence of PML. Natalizumab is a humanized monoclonal antibody targeting α4 integrins that prevents inflammatory cells from entering the brain and it has been used as a treatment for MS. A number of studies have investigated the occurrence of PML in these patients and their cell-mediated immune profile that might gain insight into the mechanism that ties natalizumab with a high risk of developing PML. It seems that cells of the immune system participate in the pathogenesis of PML as well as clearance of JCV infection.
Highlights
During the course of viral infections, cells of the immune system function to protect the host by clearing virus and infected cells from the peripheral circulation in blood and numerable tissue compartments
The immune cells within these compartments are predominantly precursor and mature T and B lymphocytes as well as multipotential stem cells of the hematopoietic system found in bone marrow
While immune system cells in human infection with JC virus do play a critical role in clearing JCV, these cells participate in the pathogenesis of infection leading to PML
Summary
During the course of viral infections, cells of the immune system function to protect the host by clearing virus and infected cells from the peripheral circulation in blood and numerable tissue compartments. In another study of hematopoietic stem cell transplant (HSCT) patients, a number of patients were viremic before transplant as measured in blood and urine samples that did not diminish for approximately 1 year after transplant While these patients had anti-JCV antibody, their humoral antibody response did not lower the presence of virus. Cell-mediated responses of both CD4 and CD8 did develop over time, but that occurred over 1 year [4] These studies further implicate bone marrow and immune system cells in the pathogenesis of viral induced PML. After several weeks of treatment, the level of CD34+ cells in the periphery was substantially higher than normal, attributed to natalizumab effects on migration of cells out of bone marrow, as previously reported [6] Another cohort of MS patients who were treated with natalizumab for over 24 months had one blood sample collected for viral analysis. Viral DNA was never detected in CD3+ population of www.frontiersin.org
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