Complexities of JC Polyomavirus Receptor-Dependent and -Independent Mechanisms of Infection

Abstract

JC polyomavirus (JCPyV) is a small non-enveloped virus that establishes lifelong, persistent infection in most of the adult population. Immune-competent patients are generally asymptomatic, but immune-compromised and immune-suppressed patients are at risk for the neurodegenerative disease progressive multifocal leukoencephalopathy (PML). Studies with purified JCPyV found it undergoes receptor-dependent infectious entry requiring both lactoseries tetrasaccharide C (LSTc) attachment and 5-hydroxytryptamine type 2 entry receptors. Subsequent work discovered the major targets of JCPyV infection in the central nervous system (oligodendrocytes and astrocytes) do not express the required attachment receptor at detectable levels, virus could not bind these cells in tissue sections, and viral quasi-species harboring recurrent mutations in the binding pocket for attachment. While several research groups found evidence JCPyV can use novel receptors for infection, it was also discovered that extracellular vesicles (EVs) can mediate receptor independent JCPyV infection. Recent work also found JCPyV associated EVs include both exosomes and secretory autophagosomes. EVs effectively present a means of immune evasion and increased tissue tropism that complicates viral studies and anti-viral therapeutics. This review focuses on JCPyV infection mechanisms and EV associated and outlines key areas of study necessary to understand the interplay between virus and extracellular vesicles.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

“…Progressive multifocal leukoencephalopathy (PML) is a rare CNS demyelinating disease caused by the JC polyomavirus (JCPyV). The virus infects immunocompromised individuals with AIDS, rheumatoid arthritis (RA), and MS. EVs derived from the epithelial cells of the choroid plexus are the prominent carriers of the virus. , The oligodendrocytes and astrocytes, the prime targets, lack the sialic acid binding-lactoseries tetrasaccharide C (LSTc) receptors, , which are required for JCPyV endocytosis, − thus making EVs the only source of JCPyV infection. Indeed, Oberholster et al characterized the EVs isolated from the human-induced pluripotent stem cell (hiPSCs)-derived astrocytes that were infected with JCPyV and observed altered levels of cell cycle and DNA damage proteins .…”

IgG Seroreactivites to Viral Capsid Protein VP1 of JC and BK Polyomaviruses in Children at Early Ages with Special Reference to Parental Cofactors

“…We also identified children and parents who remained BKPyV and JCPyV seronegative during the entire FU. Possible explanations include tolerance to these viruses or mutations in host proteins required for viral entry, infection, or both [28]. The maternal immune system and immunomodulation during pregnancy were recently described, not only at the fetal-maternal interface but also at a systemic level.…”

Investigation of Epstein–Barr virus, Cytomegalovirus, Human herpesvirus 6, and Polyoma viruses (JC virus, BK virus) among Gastric cancer patients: A cross sectional study

“…On the other hand, JCV is the PML causative agent and is related to other rare neurological complications. 13 JCV antibodies can be found in 90% of adults, except with isolated populations in South America and Papua New Guinea. JCV is typically transmitted early in life leading to a lifelong, asymptomatic infection that remains latent in the kidneys, central nervous system (CNS), and CD34+ lymphocytes.…”

“…Both viruses cause persistent infections in the kidney, but only BKV typically causes complications at this site. On the other hand, JCV is the PML causative agent and is related to other rare neurological complications 13 …”

“…On the other hand, JCV is the PML causative agent and is related to other rare neurological complications. 13 …”