Establishment of an immunoscreening system using recombinant VP1 protein for the isolation of a monoclonal antibody that blocks JC virus infection

Abstract

Polyomavirus JC (JCV) infection causes the fatal human demyelinating disease, progressive multifocal leukoencephalopathy. Although the initial interaction of JCV with host cells occurs through direct binding of the major viral capsid protein (VP1) with cell-surface molecules possessing sialic acid, these molecules have not yet been identified. In order to isolate monoclonal antibodies which inhibit attachment of JCV, we established an immunoscreening system using virus-like particles consisting of the VP1. Using this system, among monoclonal antibodies against the cell membrane fraction from JCV-permissive human neuroblastoma IMR-32 cells, we isolated a monoclonal antibody designated as 24D2 that specifically inhibited attachment and infection of JCV to IMR-32 cells. The antibody 24D2 recognized a single molecule of around 60 kDa in molecular weight in the IMR-32 membrane fraction. Immunohistochemical staining with 24D2 demonstrated immunoreactivity in the cell membrane of JCV-permissive cell lines and glial cells of the human brain. These results suggested that the molecule recognized by 24D2 plays a role in JCV infection, and that it might participate as a receptor or a co-receptor in JCV attachment and entry into the cells.

JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region

“…The emergence of human immunodeficiency virus 1 (HIV-1) infection elicited an additional interest in JCV with the frequent finding of HIV-1 carriers co-infected with JCV. 10 The incidence of PML is gradually increasing among AIDS patients, initially as a consequence of the increase of HIV-1 infections, and secondly, as an increase in life expectancy as a result of better antiretroviral drugs. 10 JCV infects HIV-1 carriers and is one of the major opportunistic infections of the central nervous system.…”

“… 10 The incidence of PML is gradually increasing among AIDS patients, initially as a consequence of the increase of HIV-1 infections, and secondly, as an increase in life expectancy as a result of better antiretroviral drugs. 10 JCV infects HIV-1 carriers and is one of the major opportunistic infections of the central nervous system. 11 , 12 , 13 , 14 , 15 In our previous study we described JCV and BKV infections among Amerindian tribes, Afro-descendant communities, as well as in the urban area of Belém, state of Para, north of Brazil.…”

Human JCV Infections as a Bio-Anthropological Marker of the Formation of Brazilian Amazonian Populations

“…The emergence of HIV-1 elicited an additional interest in JCV with the frequent finding of HIV-1 carriers infected with JCV [4].…”

“…JCV is the etiologic agent of progressive multifocal leucoencephalopathy (PML), a progressive neurological disease of the central nervous system [1] – [4] . The emergence of HIV-1 elicited an additional interest in JCV with the frequent finding of HIV-1 carriers infected with JCV [4] .…”