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Peer-reviewedCC BY 4.0Scientific Reports

Impact of Leishmania RNA virus 2 on immune response and pathogenesis in Leishmania major-infected BALB/c mice

Abstract

Leishmania RNA virus (LRV)1 has been associated with altered disease outcomes in cutaneous leishmaniasis (CL), but the role of LRV2 in Leishmania major ( L. major ) infection remains poorly understood. This study investigated the impact of LRV2-positive L. major (Lm-LRV2 ⁺ ) on disease progression and host immune responses. J774A.1 macrophages were infected with Lm-LRV2 ⁺ or LRV2 ⁻ (Lm-LRV2 ⁻ ) parasites, and cytokine gene expression was measured by qPCR. BALB/c mice were inoculated subcutaneously with either strain; lesion development was monitored weekly, and parasite burden, cytokine responses (IFN-γ, IL-4, IL-17 A), and humoral responses (IgG, IgG1, IgG2a) were assessed. Macrophages infected with Lm-LRV2 ⁺ showed significantly elevated IL-6 and IL-1β mRNA levels compared to Lm-LRV2 ⁻ ( p < 0.01). In vivo, Lm-LRV2 ⁺ infection resulted in larger lesions and higher parasite loads ( p < 0.01). Lymphocytes from Lm-LRV2 ⁺ mice produced significantly more IFN-γ, IL-4, and IL-17 A at eight weeks ( p < 0.05), and antigen-specific IgG responses and IgG2a/IgG1 ratios were also increased. These findings demonstrate that LRV2 presence in L. major enhances pro-inflammatory cytokine expression and drives a more severe disease phenotype, with notable shifts in both cellular and humoral immunity. Our results underscore the critical role of LRV2 in CL pathogenesis and suggest that viral endosymbionts may serve as important modulators of disease outcomes in Leishmania infections.

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BibTeX
@article{riazirad2026impact,
  title = {{Impact of Leishmania RNA virus 2 on immune response and pathogenesis in Leishmania major-infected BALB/c mice}},
  author = {Farhad Riazi-rad and Asal Katebi and Saeed Reza Pakzad and Soheila Ajdary},
  journal = {Scientific Reports},
  year = {2026},
  month = oct,
  doi = {10.1038/s41598-026-74490-8},
  url = {https://www.nature.com/articles/s41598-026-74490-8},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Impact of Leishmania RNA virus 2 on immune response and pathogenesis in Leishmania major-infected BALB/c mice
AU  - Farhad Riazi-rad
AU  - Asal Katebi
AU  - Saeed Reza Pakzad
AU  - Soheila Ajdary
PY  - 2026
DA  - 2026/10/02
JO  - Scientific Reports
DO  - 10.1038/s41598-026-74490-8
UR  - https://www.nature.com/articles/s41598-026-74490-8
AB  - Leishmania RNA virus (LRV)1 has been associated with altered disease outcomes in cutaneous leishmaniasis (CL), but the role of LRV2 in Leishmania major ( L. major ) infection remains poorly understood. This study investigated the impact of LRV2-positive L. major (Lm-LRV2 ⁺ ) on disease progression and host immune responses. J774A.1 macrophages were infected with Lm-LRV2 ⁺ or LRV2 ⁻ (Lm-LRV2 ⁻ ) parasites, and cytokine gene expression was measured by qPCR. BALB/c mice were inoculated subcutaneously with either strain; lesion development was monitored weekly, and parasite burden, cytokine responses (IFN-γ, IL-4, IL-17 A), and humoral responses (IgG, IgG1, IgG2a) were assessed. Macrophages infected with Lm-LRV2 ⁺ showed significantly elevated IL-6 and IL-1β mRNA levels compared to Lm-LRV2 ⁻ ( p < 0.01). In vivo, Lm-LRV2 ⁺ infection resulted in larger lesions and higher parasite loads ( p < 0.01). Lymphocytes from Lm-LRV2 ⁺ mice produced significantly more IFN-γ, IL-4, and IL-17 A at eight weeks ( p < 0.05), and antigen-specific IgG responses and IgG2a/IgG1 ratios were also increased. These findings demonstrate that LRV2 presence in L. major enhances pro-inflammatory cytokine expression and drives a more severe disease phenotype, with notable shifts in both cellular and humoral immunity. Our results underscore the critical role of LRV2 in CL pathogenesis and suggest that viral endosymbionts may serve as important modulators of disease outcomes in Leishmania infections.
SN  - 2045-2322
ER  -