Identification of miR-29a as a novel biomarker for lumpy skin disease virus exposure in cattle

ABSTRACT

Micro RNAs (miRNAs) have been implicated in the regulation of maturation, proliferation, differentiation, and activation of immune cells. In this study, we demonstrated that miR-29a antagonizes IFN-γ production at early times post-LSDV infection in cattle. miR-29a was predicted to target upstream IFN-γ regulators, and its inhibition resulted in enhanced IFN-γ production in sensitized peripheral blood mononuclear cells (PBMCs). Further, stimulation of PBMCs with LSDV antigen exhibited lower levels of miR-29a, concomitant with a potent cell-mediated immune response (CMI), characterized by an increase in LSDV-specific CD8+ T cell counts and enhanced levels of IFN-γ, which eventually facilitated virus clearance. In addition, a few immunocompromised cattle (developed secondary LSDV infection at ~ 6 months) that failed to mount a potent cell-mediated immune response, were shown to maintain higher miR-29a levels. Furthermore, as compared to the sensitized crossbred cattle, PBMCs from sensitized Rathi (a native Indian breed) animals exhibited lower levels of miR-29a along with an increase in CD8+ T cell counts and enhanced levels of IFN-γ. Finally, we analysed that a ≥ 60% decrease in miR-29a expression levels in the PBMCs of sensitized cattle correlated with a potent CMI response. In conclusion, miR-29a expression is involved in antagonizing the IFN-γ response in LSDV-infected cattle and may serve as a novel biomarker for the acute phase of LSDV infection, as well as predicting the functionality of T cells in sensitized cattle. In addition, Rathi cattle mount a more potent CMI response against LSDV than crossbred cattle.

KEYWORDS:

• miR-29a
• susceptibility
• cattle
• lumpy skin disease
• LSDV
• cell-mediated immune response

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data Availability statement

All the data are available within this manuscript.

Author contributions

N.K., B.N.T., and S.S. conceived of and designed the study. R.K., N.K., A.V., S.S., S.B., Y.C., S.D., H.K., K.N, A.B. and R.K.D. collected the samples and performed laboratory experiments. S.S., R.K., and N.K. analysed the data. N.K. wrote the primary draft of the manuscript. All authors have reviewed the manuscript.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2024.2324711

Additional information

Funding

This work was supported by the Indian Council of Agricultural Research, New Delhi [grant number IXX16675]