Asian and African lineage Zika viruses show differential replication and innate immune responses in human dendritic cells and macrophages
Laura Kakkola; Olli Vapalahti; Suvi Kuivanen; Riia Järvi; Pamela Österlund; Veera Westenius; Tatjana Avšič – Županc; Miao Jiang; Ilkka Julkunen; Rickard Lundberg; Krister Melén; Miša Korva
Asian and African lineage Zika viruses show differential replication and innate immune responses in human dendritic cells and macrophages
Laura Kakkola
Olli Vapalahti
Suvi Kuivanen
Riia Järvi
Pamela Österlund
Veera Westenius
Tatjana Avšič – Županc
Miao Jiang
Ilkka Julkunen
Rickard Lundberg
Krister Melén
Miša Korva
NATURE PUBLISHING GROUP
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042825723
https://urn.fi/URN:NBN:fi-fe2021042825723
Tiivistelmä
Zika virus (ZIKV) infections in humans are considered to be mild or subclinical. However, during the recent epidemics in the Pacific Islands and the Americas, the infection was associated with Quillain-Barre syndrome and congenital infections with fetal brain abnormalities, including microcephaly. Thus, more detailed understanding of ZIKV-host cell interactions and regulation of innate immune responses by strains of differential evolutionary origin is required. Here, we characterized the infection and immune responses triggered by two epidemic Asian/American lineage viruses, including an isolate from fetal brains, and a historical, low passage 1947 African lineage virus in human monocyte-derived dendritic cells (DCs) and macrophages. The epidemic Asian/American ZIKV replicated well and induced relatively good antiviral responses in human DCs whereas the African strain replicated less efficiently and induced weaker immune responses. In macrophages both the African and Asian strains showed limited replication and relatively weak cytokine gene expression. Interestingly, in macrophages we observed host protein degradation, especially IRF3 and STAT2, at early phases of infection with both lineage viruses, suggesting an early proteasomal activation in phagocytic cells. Our data indicates that ZIKV evolution has led to significant phenotypic differences in the replication characteristics leading to differential regulation of host innate immune responses.
Kokoelmat
- Rinnakkaistallenteet [19207]