# Impact of Selenium and Vitamin E Deficiency on Zika Virus Pathogenesis and Immune Response in Mice

**Authors:** Olukunle O. Oluwasemowo, Monica E. Graham, James B. Thissen, Aram Avila-Herrera, Jeffrey A. Kimbrel, Deepa K. Murugesh, Dina R. Weilhammer, Tanya Tanner, Nicole M. Collette, Monica K. Borucki

PMC · DOI: 10.3390/v18020177 · Viruses · 2026-01-28

## TL;DR

This study shows that selenium and vitamin E deficiency in mice weakens immune responses to Zika virus, leading to higher viral loads and worse outcomes.

## Contribution

The study reveals how antioxidant micronutrient deficiency affects Zika virus pathogenesis and immune response in a mouse model.

## Key findings

- Deficient diets reduced neutralizing antibodies and antiviral cytokines in mice infected with Zika virus.
- Higher viral RNA loads and increased mortality were observed in nutritionally deficient mice.
- Specific mutations in the E and NS3 genes were enriched in nutritionally deficient animals.

## Abstract

Micronutrient status is recognized to influence host susceptibility to viral infections, yet its impact on Zika virus (ZIKV) pathogenesis remains incompletely understood. We investigated the effects of dietary selenium and combined selenium plus vitamin E deficiency on ZIKV infection outcomes in a type I interferon α/β receptor knockout (Ifnar1−/−) murine model. Mice maintained on deficient diets exhibited significantly lower neutralizing antibody titers and reduced levels of key antiviral cytokines (IFN-γ, TNF-α, IFN-α, IFN-β, IL-12p70, CCL5) compared to controls. Correspondingly, higher viral RNA loads were detected in the brains of double-deficient mice, which also experienced greater weight loss and increased mortality. Deep sequencing revealed no major differences in overall viral genome diversity across diet groups; however, specific mutations, including V330L and D67E in the E gene, and V360I in the NS3 gene, were enriched or detected in nutritionally deficient animals. These findings suggest that antioxidant micronutrient deficiency impairs both humoral and cellular immune responses to ZIKV, potentially facilitating enhanced neuroinvasion. While the functional consequences of the identified mutations warrant further investigation, our results underscore the importance of adequate micronutrient intake for optimal antiviral defense. Further studies are needed to clarify the epidemiological significance of these observations.

## Linked entities

- **Genes:** IFNAR1 (interferon alpha and beta receptor subunit 1) [NCBI Gene 3454], e (ebony) [NCBI Gene 42521], KRAS (KRAS proto-oncogene, GTPase) [NCBI Gene 3845]
- **Chemicals:** selenium (PubChem CID 6326970), vitamin E (PubChem CID 14985)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Ifnb1 (interferon beta 1, fibroblast) [NCBI Gene 15977] {aka IFN-beta, IFNB, If1da1, Ifb}, Ifna (interferon alpha complex region) [NCBI Gene 111654] {aka Ifa, Ifa8}, Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, Il2rb (interleukin 2 receptor, beta chain) [NCBI Gene 16185] {aka CD122, IL-15Rbeta, IL15Rbeta, Il-2/15Rbeta, Il-2Rbeta, p70}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, IFNAR1 (interferon alpha and beta receptor subunit 1) [NCBI Gene 3454] {aka AVP, CRF2-1, IFN-R-1, IFN-alpha-REC, IFNAR, IFNBR}, Ccl5 (C-C motif chemokine ligand 5) [NCBI Gene 20304] {aka MuRantes, RANTES, SISd, Scya5, TCP228}, Tmprss2 (transmembrane protease, serine 2) [NCBI Gene 50528] {aka D16Ertd61e}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Ifnar1 (interferon (alpha and beta) receptor 1) [NCBI Gene 15975] {aka Ifar, Ifnar, Ifrc, Infar}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Cxcl10 (C-X-C motif chemokine ligand 10) [NCBI Gene 15945] {aka C7, CRG-2, INP10, IP-10, IP10, Ifi10}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, Cgas (cyclic GMP-AMP synthase) [NCBI Gene 214763] {aka E330016A19Rik, Mb21d1}, Selenop (selenoprotein P) [NCBI Gene 20363] {aka D15Ucla1, Se-P, Sepp1, selp}, Gpx4 (glutathione peroxidase 4) [NCBI Gene 625249] {aka GPx-4, GSHPx-4, PHGPx, mtPHGPx, snGPx}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, Selenos (selenoprotein S) [NCBI Gene 109815] {aka 1500011E07Rik, H-4, H-47, H4, H47, Sels}, Csf2 (colony stimulating factor 2 (granulocyte-macrophage)) [NCBI Gene 12981] {aka CSF, Csfgm, GMCSF, Gm-CSf, MGI-IGM}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, Prdx6-ps2 (peroxiredoxin 6 pseudogene 2) [NCBI Gene 384001] {aka Aop2-rs2, GPx*, Prdx6-rs2}, Dnase1 (deoxyribonuclease I) [NCBI Gene 13419] {aka DNaseI, Dnl1}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}
- **Diseases:** neurological and reproductive pathologies (MESH:D060737), congenital disease (MESH:D030342), Body weight loss (MESH:D001835), neurological symptoms (MESH:D009461), viremia (MESH:D014766), paralysis (MESH:D010243), microcephaly (MESH:D008831), fetal infection (MESH:D005315), neurological complications (MESH:D002493), Guillain-Barre syndrome (MESH:D020275), immune impairment (MESH:D020274), inflammation (MESH:D007249), injury to (MESH:D014947), neurological impairment (MESH:D009422), infectious disease (MESH:D003141), ZIKV Infection (MESH:D000071243), Weight loss (MESH:D015431), lethargy (MESH:D053609), Infections (MESH:D007239), Mortality (MESH:D003643), Micronutrient Deficiency (MESH:D007153), Nutritional deficiencies (MESH:D044342), tremors (MESH:D014202), viral infections (MESH:D014777), vitamin E (MESH:D014811)
- **Chemicals:** isoflurane (MESH:D007530), water (MESH:D014867), methylcellulose (MESH:D008747), Vitamin E (MESH:D014810), reactive oxygen species (MESH:D017382), lipid (MESH:D008055), Alpha-Tocopherol (MESH:D024502), agarose (MESH:D012685), CO2 (MESH:D002245), TCPa (MESH:C041190), Se (MESH:D012643), polyunsaturated fatty acid (MESH:D005231), DMEM (-), crystal violet (MESH:D005840)
- **Species:** Human immunodeficiency virus 1 (no rank) [taxon 11676], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Mus musculus (house mouse, species) [taxon 10090], Zika virus (no rank) [taxon 64320], Yellow fever virus (no rank) [taxon 11089], Coxsackievirus (species) [taxon 12066], West Nile virus (no rank) [taxon 11082], Dengue virus (no rank) [taxon 12637], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** V360I, D67N, M349V, I317T, A106T, A106V, V330L, T487M, S17N, H584Y, I317V, M487V, H584Q, V188A, V360I, D67E, T106A, M349T, V330L, N17S, D67E, I317L
- **Cell lines:** /c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103), Vero — Chlorocebus sabaeus (Green monkey), Spontaneously immortalized cell line (CVCL_0059)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12945010/full.md

## References

110 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945010/full.md

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Source: https://tomesphere.com/paper/PMC12945010