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. 2013 Dec 16:13:593.
doi: 10.1186/1471-2334-13-593.

Human papillomavirus proteins are found in peripheral blood and semen Cd20+ and Cd56+ cells during HPV-16 semen infection

Carlo Foresta  1 , Alessandro Bertoldo, Andrea Garolla, Damiano Pizzol, Silvia Mason, Andrea Lenzi, Luca De Toni
Affiliations

Human papillomavirus proteins are found in peripheral blood and semen Cd20+ and Cd56+ cells during HPV-16 semen infection

Carlo Foresta et al. BMC Infect Dis. .

Abstract

Background: Human papillomavirus (HPV) currently represents an important risk factor for cancer development and infertility in humans. Whilst binding of HPV to spermatozoa has been associated with male infertility, an investigation about the presence of HPV-DNA in non-spermatozoal semen cells is lacking. Previous findings documented the presence of HPV in peripheral blood leukocytes. The aim of this study was to investigate the expression of HPV markers in semen and blood leukocytes during HPV-16 infection.

Methods: A total of 32 subjects, 16 patients affected by HPV-16 semen infection and 16 controls, were evaluated in our andrological centre and enrolled in the study. Semen non-spermatozoal cells from all subjects were isolated and evaluated for the expression of HPV-16 markers (DNA and L1, E6 proteins) and further characterized for their molecular phenotype. Analogue determination was performed on peripheral blood mononuclear cells.

Results: The presence of HPV-DNA by FISH analysis in a round cell population from semen, confirmed to be CD45+ leukocytes, was observed. These HPV-DNA containing-cells also displayed HPV-16-E6 and HPV-16-L1 viral proteins and, upon further investigation, were found to be CD20+ and CD56+, likely phenotypes of B cells and natural killer cells (NK) respectively. In 25% of the patient group, a very small population of peripheral blood mononuclear cells was found to be positive for HPV-DNA via FISH. These cells displayed the CD20+ and CD56+ phenotype alike. None of the control subjects displayed HPV-DNA in either semen or peripheral blood.

Conclusion: Considering the role of CD20+ and CD56+ cell populations in the antiviral immune response, the detection of HPV markers on leukocytes may reflect the presence of virus particles within the endosomal compartment. However, the presence of HPV markers in circulating mononuclear cells raise concerns about the risk of developing cancers to distal organs.

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Figures

Figure 1
Figure 1
Analysis of HPV-16 markers in non-spermatozoal cells from semen samples. a: FISH analysis of HPV-16 DNA in non-spermatozoal cells from semen samples. a I epithelial and a II non epithelial positive cells. Reference brigh-fiels pictures (BF) are added as inserts. b: FISH and immunofluorescence analysis of HPV16-E6 or HPV16-L1 expression on HPV-DNA bearing non-spermatozoal cells. b I HPV16-E6 protein and b II HPV16-L1 protein positive round cells.
Figure 2
Figure 2
Immunophenotype of HPV16-bearing cells in semen round cells. a: Immunofluorescence analysis of HPV16-E6 and CD45 expression on semen round cells. b: Immunofluorescence assessment of HPV16-E6 and CD20, or CD56 expression on semen leukocytes.
Figure 3
Figure 3
Analysis of HPV-DNA in peripheral blood mononuclear cells. a: FISH analysis of HPV-DNA in peripheral blood mononuclear cells. b: PCR assessment of HPV-DNA in peripheral blood mononuclear cells from patients and controls. An example of HPV-DNA product (139–145 kDa) detectable in patients 8 and 10 (Pt8 and Pt10 respectively) and undetectable in patients 5, 7 and 12 as well as in all control subjects (Pt5, Pt7, Pt12, Ct1-5 respectively). Thiosulfate sulfurtransferase (TST) band at 202 kDa was used as an internal control.
Figure 4
Figure 4
Immunophenotype of HPV16-bearing cells in peripheral blood mononuclear cells. a: Immunofluorescence for HPV16-E6 and HPV16-L1 proteins on peripheral blood mononuclear cells. a I HPV16-E6 and a II HPV16-L1 positive mononuclear cells. b: Immunofluorescence for HPV16-E6 and CD20 or CD56 on peripheral blood mononuclear cells. b I HPV16-E6 and CD20 positive mononuclear cells. b II HPV16-E6 and CD56 positive mononuclear cells.
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