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. 2024 Aug 9;14(1):18470.
doi: 10.1038/s41598-024-68898-3.

Multi-omics analysis of antiviral interactions of Elizabethkingia anophelis and Zika virus

S Omme  1 , J Wang  2 , M Sifuna  1 , J Rodriguez  1 , N R Owusu  1 , M Goli  2 , P Jiang  2 , P Waziha  2 , J Nwaiwu  2 , C L Brelsfoard  1 , A Vigneron  3 , A T Ciota  4   5 , L D Kramer  5 , Y Mechref  2 , M G Onyangos  6
Affiliations

Multi-omics analysis of antiviral interactions of Elizabethkingia anophelis and Zika virus

S Omme et al. Sci Rep. .

Abstract

The microbial communities residing in the mosquito midgut play a key role in determining the outcome of mosquito pathogen infection. Elizabethkingia anophelis, originally isolated from the midgut of Anopheles gambiae possess a broad-spectrum antiviral phenotype, yet a gap in knowledge regarding the mechanistic basis of its interaction with viruses exists. The current study aims to identify pathways and genetic factors linked to E. anophelis antiviral activity. The understanding of E. anophelis antiviral mechanism could lead to novel transmission barrier tools to prevent arboviral outbreaks. We utilized a non-targeted multi-omics approach, analyzing extracellular lipids, proteins, metabolites of culture supernatants coinfected with ZIKV and E. anophelis. We observed a significant decrease in arginine and phenylalanine levels, metabolites that are essential for viral replication and progression of viral infection. This study provides insights into the molecular basis of E. anophelis antiviral phenotype. The findings lay a foundation for in-depth mechanistic studies.

Keywords: Elizabethkingia anopheles; Antiviral interactions; Multi-omics analysis; Zika virus.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Analysis of the impact of E. anophelis on viral replication and growth kinetics of ZIKV. Vero E6 monolayers were sequentially inoculated with either Zika virus (ZIKV) and live E. anophelis or Zika virus and E. coli. Monolayers mock infected with DMEM and ZIKV were the negative controls. At 2 dpi, the viral supernatant was harvested, and the virus was quantified by qRT-PCR. (A) The viral supernatants harvested from cell monolayers were sequentially inoculated with E. anophelis/ZIKV demonstrated an attenuated replication (unpaired t-test; P < 0.0001) compared to (B) E. coli/ZIKV (unpaired t-test; P = 0.4947). E. anophelis/ZIKV or E. coli/ZIKV supernatants harvested at 48 hpi were filtered through a 0.2 µm filter to preclude bacteria, DMEM/ZIKV was the negative control. A growth curve assay was performed utilizing RT-qPCR targeting the ZIKV NS1 region to quantify the ZIKV RNA copy numbers at 1, 2, 3, and 4 dpi. (C) E. anophelis/ZIKV samples demonstrated an attenuated replicative fitness at every time point while (D). E. coli/ZIKV samples did not show any alteration in its growth patterns and the replication was similar at every time point. The virus genome copy number values are means standard deviations (representative experiment of three biological replicates of two independent experiments). **** P</=0.0001.
Figure 2
Figure 2
Determination of the impact of E. anophelis on ZIKV infectiousness. E. anophelis/ZIKV supernatants harvested at 48 hpi were filtered through a 0.2 µm filter to preclude bacteria, and DMEM/ZIKV was used as a negative control. A total of 100 μl of each supernatant was used to inoculate Vero CCL-81 cell monolayers. E. anophelis/ZIKV demonstrated a loss in capacity to form an infective virus.
Figure 3
Figure 3
Assessment of E. anophelis on protein profile. (A) Analysis of the unsupervised principal component analysis (PCA) revealed a unique cluster of proteins associated with ZIKV/live E. anophelis samples, a few common proteins between ZIKV/live E. anophelis and Heat inactivated E. anophelis/ZIKV samples, while DMEM/ZIKV and Heat inactivated E. anophelis/ZIKV samples shared common proteins. (B) An assortment of proteins associated with viral replication was impacted in the ZIKV/live E. anophelis samples. Point coloration represents the fold change observed in E. anophelis/ZIKV samples.
Figure 4
Figure 4
Defining the repertoire of host lipids perturbed by E. anophelis. (A) The lipid profile demonstrated distinct lipids associated with ZIKV/live E. anophelis and that differed from DMEM/ZIKV and Heat inactivated E. anophelis/ZIKV (B) Interaction of ZIKV and E. anophelis results in deviations associated with lipids associated with membrane curvature such as Lysophosphatidylcholine and fatty acids associated with formation of viral replication factories. We also observed the upregulation of lipids such as sphingomyelin and ceramide, that are known to be associated with the viral membrane entry. Point coloration represents the fold change observed in E. anophelis/ZIKV samples.
Figure 5
Figure 5
Assessment of the impact of E. anophelis on metabolites. We measured a significant decrease in levels of Arginine in ZIKV/ live E. anophelis compared to DMEM/ZIKV (Mock). Arginine is an essential requirement for the replication of viruses and the progression of viral infection. Point coloration represents the fold change observed in E. anophelis/ZIKV samples.
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