Overexpression of Ki-67 and cyclins A and B1 in JC virus-infected cells of progressive multifocal leukoencephalopathy.
Both SV40 and JC virus (JCV) appropriate the host cell replicative machinery to attend to their own reproductive needs. SV40 large T antigen is able to induce the expression of cyclins A, B1, and E (but not of cylin D1) in transfected diploid cells. Whether JCV infection influences cyclin expression in a similar fashion in the setting of progressive multifocal leukoencephalopathy (PML) remains unknown. Brain lesions from 7 PML cases (4 autopsies and 3 biopsies) were immunohistochemically investigated for the expression of Ki-67 and cyclins A, B1, and D1. All 7 cases showed strong positivity for Ki-67 and cyclins A and B1 in JCV-infected oligodendrocytes and astrocytes, the nuclear immunolocalization of cyclin A being in strong contrast to the cytoplasmic distribution of cyclin B1. No immunostaining for cyclin D1 was obtained in any of the 7 cases. These findings suggest that JCV infection is associated with overexpression of Ki-67 and cyclins A and B1 in PML host glial cells. Since cyclin changes in JCV-infected cells recapitulate SV40 T antigen-associated cyclin fluctuations, it appears reasonable to think that JCV T antigen shares some of the previously described capabilities of SV40 T antigen to alter cyclin expression for the sake of viral replication.
Ariza
A
A
Department of Pathology, Hospital Germans Trias i Pujol, Autonomous University of Barcelona, Spain.
Mate
J L
JL
Isamat
M
M
Calatrava
A
A
Fernández-Vasalo
A
A
Navas-Palacios
J J
JJ
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D019938:Cyclin D1 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D016867:Immunocompromised Host; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007577:JC Virus / Q000235:genetics / Q000472:pathogenicity*; D019394:Ki-67 Antigen / Q000378:metabolism*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology
C534699:CCNB1 protein, human; D019925:Cyclin A; D019926:Cyclin B; D056744:Cyclin B1; D016213:Cyclins; D004279:DNA, Viral; D019394:Ki-67 Antigen; D019938:Cyclin D1