Abstract
The human neurotropic virus JCPyV, a member of the Polyomaviridiae family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the detection of viral sequences in medulloblastomas and glial tumors, as well as expression of the viral protein T-Antigen. Few oncogenic viruses, however, have caused so much controversy regarding their role in the pathogenesis of brain tumors, but the discovery of new Polyomaviruses that cause Merkel cell carcinomas in humans and brain tumors in racoons, in addition to the role of JCPyV in colon cancer and multiple mechanistic studies have shed much needed light on the role of JCPyV in cancer. The pathways affected by the viral protein T-Antigen include cell cycle regulators, like p53 and pRb, and transcription factors that activate pro-proliferative genes, like c-Myc. In addition, infection with JCPyV causes chromosomal damage and T-Antigen inhibits homologous recombination, and activates anti-apoptotic proteins, such as Survivin. Here we review the different aspects of the biology and physiopathology of JCPyV.
Highlights
The human neurotropic virus JCPyV is a small non-enveloped, double-stranded DNA virus that belongs to the family Polyomaviridiae
The first characterization of Progressive Multifocal Leukoencephalopathy as an entity was done by Åström et al, who was the neuropathologist at Massachusetts General Hospital, when in 1958 they described an unusual demyelinating disease affecting multiple foci of the subcortical white matter, as a fatal complication in two patients suffering from chronic lymphocytic leukemia and one with Hodgkin’s lymphoma [16]
Traditional early sero-epidemiological studies relied on hemagglutination, which was later replaced by enzyme-linked immuno-absorbent assays; the close homology among viral proteins could lead to false positive results; a recent study, which uses a novel indirect ELISA methodology with synthetic peptides that mimic the JCPyV capsid protein VP-1 and prevent cross-reactivity with other Polyomaviruses has corroborated the high rates of infection in healthy individuals [53]
Summary
The human neurotropic virus JCPyV is a small non-enveloped, double-stranded DNA virus that belongs to the family Polyomaviridiae. According to the latest taxonomic classification of the International Committee on Taxonomy of Viruses, there are 77 different species of Polyomaviruses that are divided in 4 genera, in addition to 3 others that could not be classified [1]. They infect a wide variety of birds and mammals [2]. Of these 80 described Polyomaviruses, only 13 species have been identified to infect humans [3, 4], notably JCPyV, BKPyV, SV40, and Merkel Cell Polyomavirus.
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