Molecular Analysis of JC Virus Genotypes Circulating Among the Italian Healthy Population

Abstract

JC virus (JCV) is an unique virus, but eight different JCV genotypes and various subtypes have been individuated, with a geographic distribution that has been described in general but still needs to be detailed. To define JCV genotype epidemiology in Italy, the authors collected urine from 211 healthy individuals living in Northern, Central, and Southern Continental Italy, and in the two main Italian islands. As screening, JCV DNA was searched using a polymerase chain reaction (PCR) designed to amplify the highly conserved large T (LT) antigen-coding region. Then, to define JCV genotype and trascriptional control region (TCR) organization, fragments of major capsid protein (VP1) and TCR region were amplified and subjected to nucleotide sequencing. The mean frequency of JCV viruria was of 46%, without differences among the four geographically divided groups and between females and males. JCV types 1 and 4 were the most frequently detected, whereas JCV type 2 was rare, and type 3 was found only in one subject. The low frequency of JCV type 2 contrasts with the reported high frequency of this subtype in progressive multifocal leukoencephalopathy (PML), and supports its specific role in PML. The data indicate that JCV genotype epidemiology in Italy is quite different from that of other European countries; moreover, differences between the various Italian regions have been observed. An unexpected high frequency of a new variant of JCV type 4 with a stable point mutation (C --> G) at nucleotide 1851 was found. Furthermore, all the urinary strains had a TCR showing an archetypal organization.

JC virus detection and JC virus-specific immunity in natalizumab-treated Multiple Sclerosis patients

“…Thus, urinary excretion is common in healthy Europeans [26,27], and JCV DNA viruria is detectable in about one half of healthy peoples living in Italy [28]. Notably, long-term or continuous JCV urinary excretion has been observed in 20 to 50% of healthy individuals [27], with a wide variation of the quantities of JCV excreted in urine within different subjects [29].…”

JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy

“…The molecular analysis of the JCV strains was performed only on CSF samples. JCV genotypying was accomplished by amplifying a 215‐bp fragment of the JCV VP1 gene using a single set of primers: JLP15 and JLP16 (Pagani et al, 2003). The analysis of the rearranged TCR regions was performed using a previously described protocol (Delbue et al, 2005a) and the primers JRE1 and LP2 (outer) and RFOR and RREV (inner), which amplify a 353‐bp fragment belonging to the JCV TCR.…”

Association between the JC Polyomavirus Infection and Male Infertility

“…The frequency of BKV excretion in healthy individuals as reported by different studies is negligible [13]. A molecular analysis of JCV types excreted by healthy individuals in Italy, while confirming a high prevalence (46%) of JCV in urine samples, indicated that types 1 and 4 were frequent, whereas type 2 and 3 were very rare [14], [15]. Point mutations in the genes encoding the major viral capsid protein, VP1, is considered sufficient to define the eight JCV types/genotypes and the different related subtypes [16].…”

“…This result is in agreement with epidemiologic data reporting JCV genotype 1 as the most common JCV strain circulating in Italy. [14] The significance of the higher prevalence of JCV strain 2b in samples from infertile males deserves more evaluation. The potential higher pathogenicity and virulence of genotype 2, regarding both subtypes a and b, was recently described by different teams in distinct groups of immunocompromised patients [37], [38].…”