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Human cytomegalovirus (HCMV) long-term shedding and HCMV-specific immune response in pregnant women with primary HCMV infection

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Abstract

Human cytomegalovirus (HCMV) shedding has been extensively investigated in newborns and in young children, however, much less is known about it in immunocompetent adults. Shedding of HCMV was investigated in saliva, vaginal secretions and urine of pregnant women experiencing primary infection along with the development of the HCMV-specific immune response. Thirty-three pregnant women shed HCMV DNA in peripheral biological fluids at least until one year after onset of infection, while in blood HCMV DNA was cleared earlier. Significantly higher levels of viral load were found in vaginal secretions compared to saliva and urine. All subjects examined two years after the onset of infection showed a high avidity index, with IgM persisting in 36% of women. Viral load in blood was directly correlated with levels of HCMV-specific IgM and inversely correlated with levels of IgG specific for the pentameric complex gH/gL/pUL128L; in addition, viral load in blood was inversely correlated with percentage of HCMV-specific CD4+ and CD8+ expressing IL-7R (long-term memory, LTM) while viral load in biological fluids was inversely correlated with percentage of HCMV-specific CD4+ and CD8+ effector memory RA+(TEMRA). In conclusion, viral shedding during primary infection in pregnancy persists in peripheral biological fluids for at least one year and the development of both antibodies (including those directed toward the pentameric complex) and memory T cells are associated with viral clearance.

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Acknowledgements

We thank Professor Giuseppe Gerna for revision of the manuscript and helpful discussion; Valentina Marazzi and Stefania Piccini for collecting the samples.

Funding

This work was supported by Ministero della Salute, Ricerca Corrente [grant number 053618].

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Authors and Affiliations

  1. Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy

    C. Fornara, F. Zavaglio, M. Furione, A. Sarasini, D. Lilleri & F. Baldanti

  2. Obstetrics and Gynecology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    P. d’Angelo, A. Arossa & A. Spinillo

  3. Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

    A. Spinillo & F. Baldanti

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  1. C. Fornara
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Contributions

CF analyzed data and wrote the manuscript. FZ e Pd’A collected the data and performed the experiments. AS supervised the data on antibody response. MF and AA enrolled and followed the patients and provided clinical data. DL conceived the study and revised the study. FB and AS revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to D. Lilleri.

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The authors declare no conflict of interests.

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The study was approved by the local Ethics Committee (P-20180075214). Informed consent was obtained from all partecipants included in the study.

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Communicated by Matthias J. Reddehase.

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Fornara, C., Zavaglio, F., Furione, M. et al. Human cytomegalovirus (HCMV) long-term shedding and HCMV-specific immune response in pregnant women with primary HCMV infection. Med Microbiol Immunol 211, 249–260 (2022). https://doi.org/10.1007/s00430-022-00747-4

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