Detection of JC Virus DNA in Human Tonsil Tissue: Evidence for Site of Initial Viral Infection

Abstract

Progressive multifocal leukoencephalopathy is a demyelinating disease of the human central nervous system that results from lytic infection of oligodendrocytes by the polyomavirus JC (JCV). Originally, JCV was thought to replicate exclusively in human glial cells, specifically oligodendrocytes. However, we have recently shown that JCV can replicate in cells of lymphoid origin such as hematopoietic precursor cells, B lymphocytes, and tonsillar stromal cells. To determine whether tonsils harbor JCV, we tested a total of 54 tonsils, 38 from children and 16 from adult donors. Nested PCRs with primer sets specific for the viral T protein and regulatory regions were used for the detection of JCV DNA. JCV DNA was detected in 21 of 54 tonsil tissues, or 39% (15 of 38 children and 6 of 16 adults) by using regulatory-region primers and in 19 of 54 tonsil tissues, or 35% (13 of 38 children and 6 of 16 adults) by using the T-protein primers. The DNA extracted from children’s nondissected tonsil tissue, isolated tonsillar lymphocytes, and isolated stromal cells that demonstrated PCR amplification of the JCV regulatory region underwent cloning and nucleotide sequencing. Of the regulatory-region sequences obtained, nearly all contained tandem repeat arrangements. Clones originating from nondissected tonsil tissue and tonsillar lymphocytes were found to have sequences predominantly of the Mad-1 prototype strain, whereas the majority of clones from the DNA of tonsillar stromal cells had sequences characteristic of the Mad-8br strain of JCV. A few clones demonstrated structures other than tandem repeats but were isolated only from tonsillar lymphocytes. These data provide the first evidence of the JCV genome in tonsil tissue and suggest that tonsils may serve as an initial site of viral infection.

Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency

“…Furthermore, we showed widespread occurrence of MCPyV DNA in tonsillar tissue. This may be a general feature of human polyomaviruses, as tonsillar tissues can harbor both JCV 21 and BKV 22 DNA and tonsillar stromal cells have been shown to be susceptible to JCV infection. 23 Blood cellderived MCPyV positivity of the tonsils could not be completely ruled out as only serum samples (all of which tested negative for MCPyV DNA) obtained at the time of operation were available from our tonsillectomy patients.…”

Identification of archetype and rearranged forms of BK virus in leukocytes from healthy individuals

“…The tonsils have been proposed to be a primary site of infection for the human polyomaviruses based upon the detection of BKV and JCV in this tissue and upon the ability of JCV to replicate in cultures of tonsillar stromal cells [Goudsmit et al, 1982;Monaco et al, 1996Monaco et al, , 1998]. The detection of the same rearranged form, BKV(TU), in leukocytes (this study) and in urine [Sundsfjord et al, 1990], strengthens the hypothesis that lymphocyte-mediated transport of rearranged BKV variants occurs from a primary site of infection (e.g., tonsils) to secondary sites (e.g., kidney) within the body.…”

WU Polyomavirus (WUPyV): A Recently Detected Virus Causing Respiratory Disease?

“…Respiratory transmission has been suggested for JC virus and BK virus although the diseases related to these viruses are not involving the respiratory tract. Both viruses can be extracted from tonsil tissue [13,14]. The viral entry route for WUPyV is not completely defined.…”