Study of camelpox virus pathogenesis in athymic nude mice

Area of Science:

• Virology
• Immunology
• Infectious Diseases

Background:

• Camelpox virus (CMLV) is closely related to variola virus, the cause of smallpox.
• Recent human cases highlight the need for CMLV research, but a lack of animal models hinders pathogenesis studies.
• Previous studies indicated CMLV is restricted to camelids.

Purpose of the Study:

• To establish and characterize small animal models for CMLV infection.
• To investigate CMLV pathogenesis and immune responses in different mouse models.
• To evaluate the efficacy of antiviral treatments against CMLV.

Main Methods:

• Intranasal (i.n.) and intracutaneous (i.c.) CMLV challenges in NMRI immunocompetent and athymic nude mice.
• Monitoring of disease progression, weight changes, and CMLV replication in tissues and fluids.
• Analysis of innate immune cells (macrophages, neutrophils, NK cells) and B cell responses in spleen and lymph nodes.
• Quantification of cytokine profiles (IL-6, IL-18) in sera.
• Evaluation of antiviral efficacy using cidofovir and HPMPC.

Main Results:

• Athymic nude mice developed severe disease after i.n. CMLV infection, unlike resistant immunocompetent mice.
• CMLV replicated in tissues and fluids of both mouse models, with varying immune cell responses depending on infection route.
• HPMPC demonstrated 100% protection against CMLV-induced morbidity without affecting immune responses or cytokine levels.

Conclusions:

• Immunodeficient mice are permissive to CMLV, providing a viable model for pathogenesis research.
• This model facilitates the evaluation of antiviral therapies for CMLV in an immunodeficient context.
• HPMPC shows significant promise as an effective antiviral agent against CMLV.