Intra-host evolution during relapsing parvovirus B19 infection in immunocompromised patients

medRxiv

Abstract

Abstract Introduction Parvovirus B19 (B19V) can cause severe relapsing episodes of anemia in immunocompromised individuals, which are commonly treated with intravenous immunoglobulins (IVIG). Few data is available on B19V intra-host evolution and the role of humoral immune selection. Here, we report the dynamics of genomic mutations and subsequent protein changes during relapsing infection. Methods Longitudinal plasma samples from immunocompromised patients with relapsing B19V infection in the period 2011-2019 were analyzed using whole genome sequencing to evaluate intra-host evolution. The impact of mutations on the 3D viral protein structure was predicted by deep neural network modeling. Results Of the three immunocompromised patients with relapsing infections for 3 to 9 months, one patient developed two consecutive nonsynonymous mutations in the VP1/2 region: T372S/T145S, and Q422L/Q195L. The first mutation was detected in multiple B19V IgG seropositive follow-up samples, and resolved after IgG seroreversion. Computational prediction of the VP1 3D structure of this mutant showed a conformational change in proximity of the antibody binding domain. No conformational changes were predicted for the other mutations detected. Discussion Analysis of relapsing B19V infections showed mutational changes occurring over time. Resulting amino acid changes were predicted to lead to a conformational capsid protein change in an IgG- seropositive patient. The impact of humoral response and IVIG treatment on B19V infections should be further investigated to understand viral evolution and potential immune escape.

Authors 9

1. Anne Russcher corresponding Aachen LUCID Medical Microbiology and Infection Control

   Leiden University Medical Center

   Affiliation as printed

   LUCID Medical Microbiology and Infection Control, Leiden University Medical Center, Leiden, the Netherlands

2. Yassene Mohammed Aachen Center for Proteomics and Metabolomics

   Leiden University Medical Center

   Affiliation as printed

   Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands

3. Margriet E. M. Kraakman Aachen LUCID Medical Microbiology and Infection Control

   Leiden University Medical Center

   Affiliation as printed

   LUCID Medical Microbiology and Infection Control, Leiden University Medical Center, Leiden, the Netherlands

4. Xavier Chow Aachen Center for Proteomics and Metabolomics

   Leiden University Medical Center

   Affiliation as printed

   Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands

5. Eric C. J. Claas Aachen LUCID Medical Microbiology and Infection Control

   Leiden University Medical Center

   Affiliation as printed

   LUCID Medical Microbiology and Infection Control, Leiden University Medical Center, Leiden, the Netherlands

6. Manfred Wuhrer Aachen Center for Proteomics and Metabolomics

   Leiden University Medical Center

   Affiliation as printed

   Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands

7. Ann C.T.M. Vossen Aachen LUCID Medical Microbiology and Infection Control

   Leiden University Medical Center

   Affiliation as printed

   LUCID Medical Microbiology and Infection Control, Leiden University Medical Center, Leiden, the Netherlands

8. Aloys C.M. Kroes Aachen LUCID Medical Microbiology and Infection Control

   Leiden University Medical Center

   Affiliation as printed

   LUCID Medical Microbiology and Infection Control, Leiden University Medical Center, Leiden, the Netherlands

9. Jutte J.C. de Vries Aachen LUCID Medical Microbiology and Infection Control

   Leiden University Medical Center

   Affiliation as printed

   LUCID Medical Microbiology and Infection Control, Leiden University Medical Center, Leiden, the Netherlands