An Elusive Target: Inhibitors of JC Polyomavirus Infection and Their Development as Therapeutics for the Treatment of Progressive Multifocal Leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by infection with JC Polyomavirus (JCPyV). Despite the identification of the disease and isolation of the causative pathogen over fifty years ago, no antiviral treatments or prophylactic vaccines exist. Disease onset is usually associated with immunosuppression, and current treatment guidelines are limited to restoring immune function. This review summarizes the drugs and small molecules that have been shown to inhibit JCPyV infection and spread. Paying attention to historical developments in the field, we discuss key steps of the virus lifecycle and antivirals known to inhibit each event. We review current obstacles in PML drug discovery, including the difficulties associated with compound penetrance into the central nervous system. We also summarize recent findings in our laboratory regarding the potent anti-JCPyV activity of a novel compound that antagonizes the virus-induced signaling events necessary to establish a productive infection. Understanding the current panel of antiviral compounds will help center the field for future drug discovery efforts.

JCV seroconversion rate during the SARS COVID-19 pandemic.

The transmission route of the John Cunningham virus (JCV) is not clearly understood. The high prevalence of JCV in urine and sewage and the stability of the viral particles observed suggest that contaminated water, food, and fomites could be the vehicles of JCV transmission through the oral route. Multiple Sclerosis (MS) patients treated with Natalizumab are at risk of developing progressive multifocal leukoencephalopathy (PML), and hence, JCV serology is monitored for risk stratification. Social restrictions introduced in 2020 which intended to limit the transmission of SARS-CoV-2 are associated with decreased rates of other communicable diseases, as has been shown in recent observational studies. We evaluated the prevalence of seroconversion prior to and during the coronavirus disease (COVID -19) pandemic based on clinical records of JCV serology status in a single-center cohort of Natalizumab-treated Multiple Sclerosis patients. We hypothesized that seroconversion rates would decrease due to behavioral changes. However, seroconversion rates were stable during the COVID-19 pandemic compared to the pre-pandemic. These findings support the notion that JCV is transmitted via the GI tract rather than the respiratory system.

JC virus-induced progressive multifocal leukoencephalopathy in a presumably healthy patient.

BACKGROUND: JC virus (JCV) is common among healthy individuals and remains latent but may be reactivated under immunosuppressive conditions, resulting in progressive multifocal leukoencephalopathy (PML). Here, we present a rare case of PML caused by JC virus infection in a previously healthy and immunocompetent patient. CASE PRESENTATION: A 67-year-old female without any disease history was admitted after presenting with rapidly progressive dementia. The preoperative diagnosis was progressive multifocal leukoencephalopathy, and corticosteroid treatment did not improve the symptoms. Brain lesions were surgically sampled, and JCV infection was confirmed by high-throughput DNA gene detection. This patient received a combined treatment of mirtazapine, mefloquine, and traditional Chinese herbs, and had stabilization of the disease on followed-up. CONCLUSIONS: Although it is a rare, this case demonstrates that JC virus infection within the brain occurs in apparently healthy people. This case may increase our understanding of virus infection when facing the coronavirus epidemic in recent years, considering that similar medications were used.

Progressive multifocal leukoencephalopathy in an immunocompetent patient: A case report and review of literature.

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, caused by the John Cunningham virus (JCV) is usually seen in patients who are immunocompromised. Here, we describe a case of an immunocompetent patient diagnosed with PML and a comprehensive literature review. A 64-year-old Caucasian male presented with acute worsening of progressive neurological decline with difficulty in vision and reading. Based on history, examination, cerebrospinal fluid markers, histopathology, and magnetic resonance imaging brain at the time of presentation diagnosed the patient with PML in a setting of no immunosuppression disorder. The patient was started on Pelfilgrastim with significant systematic improvement. In our literature review, it was seen that the average age of symptom presentation was 57.5 with predominance in males. Most of the patients presented with progressive neurological deficits with symptomology ranging from mild confusion, aphasia, anxiety to sensory disturbances with numbness, hemiparesis, and hemianopsia. Out of the 21 cases, patients responded to mirtazapine and intravenous pulse methylprednisolone (IVMP). The mortality rate was close to 50% with 11 fatal cases and 10 nonfatal cases. Our case and literature review demonstrate the possibility that PML may very rarely occur in patients that are immunocompetent. Furthermore, our review showed that patients responded well to mirtazapine and IVMP. We also want to highlight that the mortality rate was lower in this review and was only compared to mortality in PML associated with immunocompromised status.