High-fat diet exacerbates SIV pathogenesis and accelerates disease progression

Area of Science:

• Immunology
• Virology
• Nutritional Science

Background:

• High-fat diets (HFD) are linked to obesity, diabetes, and systemic inflammation, conditions that share similarities with Human Immunodeficiency Virus (HIV) infection.
• HFD can cause intestinal dysbiosis, impair liver function, and affect coagulation, potentially worsening HIV/Simian Immunodeficiency Virus (SIV) pathogenesis.

Purpose of the Study:

• To investigate the impact of a high-fat diet on SIV disease progression in nonpathogenic and pathogenic SIV hosts.
• To determine how HFD affects viral reservoirs, immune activation, inflammation, and metabolic disturbances in the context of SIV infection.

Main Methods:

• Administered a HFD rich in saturated fats and cholesterol to African green monkeys (nonpathogenic SIV host) and pigtailed macaques (pathogenic SIV host).
• Assessed viral DNA/RNA, immune cell infiltration in adipose tissue, systemic immune activation, inflammation, gut integrity, microbial translocation, lipid metabolism, and cardiovascular risk markers.

Main Results:

• HFD exacerbated SIV disease progression in both species, evidenced by increased cell-associated SIV DNA and RNA, suggesting reservoir expansion.
• HFD induced significant immune cell infiltration in adipose tissue, heightened systemic immune activation and inflammation, and altered the intestinal immune environment, leading to gut damage and microbial translocation.
• Metabolic disturbances, including altered lipid metabolism, HDL oxidation, liver steatosis, fibrosis, incipient atherosclerosis, and increased cardiovascular risk, were observed in SIV-infected nonhuman primates on HFD.

Conclusions:

• Dietary intake significantly impacts the natural history of HIV/SIV infections.
• Dietary interventions may serve as adjuvant therapies for HIV-infected individuals to mitigate inflammation, reduce non-AIDS comorbidities, and potentially impact other infectious diseases.