Persistence and Intra-Host Genetic Evolution of Zika Virus Infection in Symptomatic Adults: A Special View in the Male Reproductive System

Danielle  B. L. Oliveira; Giuliana  S. Durigon; Érica  A. Mendes; Jason  T. Ladner; Robert Andreata-Santos; Danielle  B. Araujo; Viviane  F. Botosso; Nicholas  D. Paola; Daniel  F. L. Neto; Marielton  P. Cunha; Carla  T. Braconi; Rúbens  P. S. Alves; Monica  R. Jesus; Lennon  R. Pereira; Stella  R. Melo; Flávio  S. Mesquita; Vanessa  B. Silveira; Luciano  M. Thomazelli; Silvana  R. Favoretto; Franciane  B. Almonfrey; Regina  C. R. M. Abdulkader; Joel  M. Gabrili; Denise  V. Tambourgi; Sérgio  F. Oliveira; Karla Prieto; Michael  R. Wiley; Luís  C. S. Ferreira; Marcos  V. Silva; Gustavo  F. Palacios; Paolo  M. A. Zanotto; Edison  L. Durigon

doi:10.3390/v10110615

Viruses (Nov 2018)

Persistence and Intra-Host Genetic Evolution of Zika Virus Infection in Symptomatic Adults: A Special View in the Male Reproductive System

Danielle B. L. Oliveira,
Giuliana S. Durigon,
Érica A. Mendes,
Jason T. Ladner,
Robert Andreata-Santos,
Danielle B. Araujo,
Viviane F. Botosso,
Nicholas D. Paola,
Daniel F. L. Neto,
Marielton P. Cunha,
Carla T. Braconi,
Rúbens P. S. Alves,
Monica R. Jesus,
Lennon R. Pereira,
Stella R. Melo,
Flávio S. Mesquita,
Vanessa B. Silveira,
Luciano M. Thomazelli,
Silvana R. Favoretto,
Franciane B. Almonfrey,
Regina C. R. M. Abdulkader,
Joel M. Gabrili,
Denise V. Tambourgi,
Sérgio F. Oliveira,
Karla Prieto,
Michael R. Wiley,
Luís C. S. Ferreira,
Marcos V. Silva,
Gustavo F. Palacios,
Paolo M. A. Zanotto,
Edison L. Durigon

Affiliations

Danielle B. L. Oliveira: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Giuliana S. Durigon: Medical School Clinic Hospital, University of São Paulo, São Paulo, SP 05403-000, Brazil
Érica A. Mendes: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Jason T. Ladner: Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
Robert Andreata-Santos: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Danielle B. Araujo: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Viviane F. Botosso: Virology Laboratory, Butantan Institute, São Paulo, SP 05503-900, Brazil
Nicholas D. Paola: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Daniel F. L. Neto: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Marielton P. Cunha: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Carla T. Braconi: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Rúbens P. S. Alves: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Monica R. Jesus: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Lennon R. Pereira: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Stella R. Melo: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Flávio S. Mesquita: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Vanessa B. Silveira: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Luciano M. Thomazelli: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Silvana R. Favoretto: Pasteur Institute, State Health Department, São Paulo, SP 1103-000, Brazil
Franciane B. Almonfrey: Medical School Clinic Hospital, University of São Paulo, São Paulo, SP 05403-000, Brazil
Regina C. R. M. Abdulkader: Medical School Clinic Hospital, University of São Paulo, São Paulo, SP 05403-000, Brazil
Joel M. Gabrili: Virology Laboratory, Butantan Institute, São Paulo, SP 05503-900, Brazil
Denise V. Tambourgi: Virology Laboratory, Butantan Institute, São Paulo, SP 05503-900, Brazil
Sérgio F. Oliveira: Department of Cellular and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Karla Prieto: Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
Michael R. Wiley: Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
Luís C. S. Ferreira: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Marcos V. Silva: Institute of Infectology Emílio Ribas e Pontifícia Universidade Católica (PUC-SP), São Paulo, SP 01246-900, Brazil
Gustavo F. Palacios: Center for Genome Sciences, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA
Paolo M. A. Zanotto: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil
Edison L. Durigon: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil

DOI: https://doi.org/10.3390/v10110615
Journal volume & issue: Vol. 10, no. 11
p. 615

Abstract

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We followed the presence of Zika virus (ZIKV) in four healthy adults (two men and two women), for periods ranging from 78 to 298 days post symptom onset. The patients were evaluated regarding the presence of the virus in different body fluids (blood, saliva, urine and semen), development of immune responses (including antibodies, cytokines and chemokines), and virus genetic variation within samples collected from semen and urine during the infection course. The analysis was focused primarily on the two male patients who shed the virus for up to 158 days after the initial symptoms. ZIKV particles were detected in the spermatozoa cytoplasm and flagella, in immature sperm cells and could also be isolated from semen in cell culture, confirming that the virus is able to preserve integrity and infectivity during replication in the male reproductive system (MRS). Despite the damage caused by ZIKV infection within the MRS, our data showed that ZIKV infection did not result in infertility at least in one of the male patients. This patient was able to conceive a child after the infection. We also detected alterations in the male genital cytokine milieu, which could play an important role in the replication and transmission of the virus which could considerably increase the risk of ZIKV sexual spread. In addition, full genome ZIKV sequences were obtained from several samples (mainly semen), which allowed us to monitor the evolution of the virus within a patient during the infection course. We observed genetic changes over time in consensus sequences and lower frequency intra-host single nucleotide variants (iSNV), that suggested independent compartmentalization of ZIKV populations in the reproductive and urinary systems. Altogether, the present observations confirm the risks associated with the long-term replication and shedding of ZIKV in the MRS and help to elucidate patterns of intra-host genetic evolution during long term replication of the virus.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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