Footprints of BK and JC polyomaviruses in specimens from females affected by spontaneous abortion

Abstract

Study question: Are JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) infections associated with spontaneous abortion (SA)?

Summary answer: There is no association of JCPyV or BKPyV with SA.

What is known already: A large number of risk factors have been associated with SA. The role of polyomaviruses, including JCPyV and BKPyV, in SA remains to be clarified.

Study design, size, duration: This is a case-control study including women affected by spontaneous abortion (SA, n = 100, the cases) and women who underwent voluntary interruption of pregnancy (VI, n = 100, the controls).

Participants/materials, setting, methods: Viral DNAs were investigated by qualitative PCR and quantitative droplet-digital PCR (ddPCR) in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from SA (n = 100) and VI (n = 100). Indirect ELISAs with mimotopes/synthetic peptides corresponding to JCPyV and BKPyV viral capsid protein 1 epitopes were then employed to investigate specific IgG antibodies against JCPyV and BKPyV in human sera from SA (n = 80) and VI (n = 80) cohorts.

Main results and the role of chance: JCPyV DNA was detected in 51% and 61% of SA and VI samples, respectively, with a mean viral DNA load of 7.92 copy/104 cells in SA and 5.91 copy/104 cells in VI (P > 0.05); BKPyV DNA was detected in 11% and 12% of SA and VI specimens, respectively, with a mean viral DNA load of 2.7 copy/104 cells in SA and 3.08 copy/104 cells in VI (P > 0.05). JCPyV was more prevalent than BKPyV in both SA and VI specimens (P < 0.0001). In PBMCs from the SA and VI cohorts, JCPyV DNA was detected with a prevalence of 8% and 12%, respectively, with a mean viral DNA load of 2.29 copy/104 cells in SA and 1.88 copy/104 cells in VI (P > 0.05). The overall prevalence of serum IgG antibodies against JCPyV detected by indirect ELISAs was 52.5% and 48.7% in SA and VI groups, respectively, whereas BKPyV-positive sera were found in 80% SA and 78.7% VI samples.

Limitations, reasons for caution: This study did not investigate the presence of viral mRNA and/or proteins, which are indicative of an active viral infection, and these might be taken into consideration in future studies.

Wider implications of the findings: JCPyV and BKPyV DNA sequences were detected and quantitatively analyzed for the first time by PCR/ddPCR in chorionic villi tissues and PBMCs from SA and VI specimens. Moreover specific immunological approaches detected serum IgG against JCPyV/BKPyV. Statistical analyses, however, do not indicate an association between these polyomaviruses and SA.

Study funding/competing interest(s): This work was supported by the University of Ferrara, FAR research grants and the University Hospital of Ferrara/University of Ferrara joint grant. No potential conflicts of interest were disclosed.

Keywords: BKPyV; ELISA; JCPyV; PCR; droplet-digital PCR; miscarriage; polyomavirus; pregnancy; viral DNA load.