Spectrum of Diseases Affecting the Nervous System Associated with JC - Virus: A Review

Review Article

Austin J Infect Dis. 2023; 10(3): 1090.

Spectrum of Diseases Affecting the Nervous System Associated with JC - Virus: A Review

Andonova RS1*; Bashchobanov DzhH1,2; Slavcheva BG1; Gadzhovska VP1; Dragusheva ES1; Marinova RV1; Angelova MCh1; Popov GT1

¹Department of Infectious Diseases, Sofiamed Hospital, Sofia, Bulgaria

²Medical Faculty, Medical University of Sofia, Bulgaria

*Corresponding author: Andonova RS Department of Infectious Diseases, Sofiamed Hospital, 10 St Mollov Dimitar, Bulgaria. Tel: +359-878-775-193 Email: radina6@mail.bg

Received: August 19, 2023 Accepted: September 30, 2023 Published: October 07, 2023

Abstract

The JC polyomavirus (JCPyV) belongs to the family Polyomaviridae, genus Betapolyomavirus. These are small, non-enveloped, double-stranded DNA viruses. Approximately 60-80% of the population is carriers of JC polyomavirus. Various ways of spread are being studied. These viruses are associated with a large spectrum of neurological diseases, including progressive multifocal leukoencephalopathy, JC-associated meningitis and encephalitis, JCV granule cell neuronopathy and numerous central nervous system malignancies. In the majority of individuals, the virus remains latent in the kidney tissue. However, in certain subgroups, it leads to the development of severe and frequently disabling or fatal diseases. These subgroups are usually immunosuppressed, which causes the virus to undergo lytic rearrangement. Understanding these diseases and the mechanisms by which they occur is paramount for making accurate diagnoses. Studying these diseases is necessary to develop effective treatments and limit their harmful effects.

Keywords: JC: Polyomavirus; Neurolocigal diseases; PML; JC: Meningitis; JC: Encephalitis

Abbreviations: JCPyV: JC Polyomavirus; PML: Progressive Multifocal Leukoencephalopathy; JCVE, JCVM: JC-Associated Meningitis and Encephalitis; JCV GCN: JCV Granule Cell Neuronopathy; HD: Hodgkin’s Disease; BKV: BK-Virus; SV40: Simian Virus 40; MCPyV: Merkel Cell Polyomavirus; NCCR: Non-Coding Control Region; CNS: Central Nervous System; CSF: Cerebro-Spinal Fluid; LTAg: Large Tumor Antigen; stAg: Small Tumor Antigen

Introduction

In 1963, Zu Rhein & Chou, using an electron microscope and laboratory tests, were able to isolate and prove the presence of the JC virus (JCPyV) from the brain of a person with Hodgkin's Disease (HD) [1]. The virus was associated with the disease - Progressive Multifocal Encephalopathy (PML), first described in 1958 by Å Åströ ööööööööööööööööm et al, in patients with HD and Chronic Lymphocytic Leukemia (CLL) [2]. JCV belongs to the genus polyomavirus, which also includes BK Virus (BKV), SIMIAN VIRUS 40 (SV40), and Merkel Cell Polyomavirus (MCPyV) [3,4]. Polyomaviruses are small, non-enveloped icosahedral capsid viruses containing a circular DNA molecule [3-5]. Their genome is composed of three parts - two coding (early and late) and one noncoding. The early coding region is transcribed before replication and encodes the Large (LTAg) and Small Tumor Antigen (stAg), the Non-Coding Control Region (NCCR) is located between the early and late coding regions and contains enhancers/promoters for their expression. There are two types of JSPyV- Archetype (RR-JCPyV) and Mad-1, which differ in the structure of the NCCR. Archetype is transmitted in humans and is the most common type in the environment. The late control region is transcribed after replication and encodes the structural viral proteins (VP1, VP2, VP3) as well as the small accessory protein (Agno) [5-10]. 60 years after the discovery of JC virus, the aim of our review is to present the associated neurological diseases described in the world literature.

Primary Infection

It is difficult to determine the period of primary JCV infection due to the asymptomatic nature of the infection. Approximately 8-10% of children are seropositive by their first six years [5], this percentage increases to 50% in 10-15 year old children, and in adulthood approximately 80% of individuals are infected [4,5]. Based on genotypic analysis, JCV has been found to be transmitted within the family [5,11]. DNA sequence of JCV is found in tonsils, gastrointestinal tract, it is also possible to be isolated from CSF [5]. This also suggests a possible mechanism of transmission via fecal-oral route and tonsillar tissue [13]. Mazzoni et al. in their study commented on the possibility of mother-to-child transmission [14]. Mopes et al. also present a suggestion of a possible inhalation route of infection [15]. The virus is most commonly isolated in the urine and this is thought to be the main route of spread, but there is as yet no conclusive evidence for this. Primary infection has been suggested to be spread by the haematogenous route [5,12], and the virus may remain latent or persistent in the tonsils, kidneys, spleen, bone marrow, heart, and lungs. Monaco et al. isolated JCPyV DNA from tonsillar tissue and reported that stromal cells were more sensitive than B lymphocytes and CDC34+ cells to JCPyV [15].

RR-JCPyV is the transmissible form of the virus, it is nonpathogenic. After extensive genomic rearrangement of NCCR, the pathogenic PML-type/Mad-1 form of the virus is produced, which exhibits neurotropicity [13]. When there is an immunosuppression, for example in HIV infection or autoimmune diseases treated with immunomodulatory therapy, the JC virus is reactivated, and can reach the brain via B lymphocytes. However, viral DNA has also been isolated from brains of immunocompetent patients, suggesting that it is an organ where the virus can enter without having undergone genomic rearrangement and remain there in a latent state [16]. Sixty years after JCPyV was first isolated, we now know more about its structure, primary infection, latent state, and the spectrum of diseases associated with it. After reactivation, the virus can affect cerebral oligodendrocytes and astrocytes, leading to progressive multifocal leukoencephalopathy [15-17] In their review, Miskin and Koralnik describe that JCPyV can also affect cerebellar granule cell neurons, cerebral cortical pyramidal neurons, and meningeal and choroid plexi cells, leading to JCV granule cell neuronopathy (JCV GCN), JCV encephalopathy (JCVE), and JCV meningitis (JCVM) [18,19] (Figure 1).

Citation: Andonova RS, Bashchobanov DzhH, Slavcheva BG, Gadzhovska VP, Dragusheva ES, et al. Spectrum of Diseases Affecting the Nervous System Associated with JC - Virus: A Review. Austin J Infect Dis. 2023; 10(3): 1090.