Immunosuppression increases latent infection of brain by JC polyomavirus

Aims: 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. Methods: 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. Results: 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). Conclusions: Immunosuppression drives increased brain JCV latency independent of systemic latency.