Immunosuppression increases latent infection of brain by JC polyomavirus

Abstract

Progressive multifocal leukoencephalopathy (PML) is caused by reactivation of JC polyomavirus (JCV). Increased JCV reactivation in kidney, as indicated by JCV viruria is reported during immunosuppression; however, the relevance of systemic to neural reactivation remains unknown. Brain and kidney tissue from 138 non-PML patients (78 immunocompetent; 60 immunosuppressed) was assessed for JCV large T (LT) and viral protein (VP)1 DNA with nested PCR. Immunohistochemistry was performed to detect presence of JCV protein. Autopsy findings were reviewed and all brains underwent neuropathological examination. JCV LT DNA was detected in 31% of kidney and 30% of brain from non-PML patients. Of non-PML patients with brain JCV LT DNA, 66% did not have kidney JCV LT DNA, indicating brain JCV LT DNA was independent of kidney JCV LT DNA (p = 0.69). JCV VP1 DNA was detected in 12% of non-PML kidney and 8% of non-PML brain. JCV LT DNA was more likely to be found in the kidney (p < 0.001) and brain (p = 0.009) of immunosuppressed than immunocompetent patients. HIV/AIDS patients with brain JCV LT DNA had lower CD4 counts than those without brain JCV LT DNA (p = 0.05). Immunosuppression drives increased brain JCV latency independent of systemic latency.