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Anti-viral defense by natural microbial environmental agents

Award Number: R56AI201174
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/12/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Anti-viral defense by natural microbial environmental agents - This application seeks to characterize the mechanisms through which natural environmental agents from traditional Amish farms protect the lung against rhinovirus (RV), a respiratory pathogen strongly associated with the development of asthma, one of the most common chronic diseases of childhood. Children raised on traditional farms are protected from asthma. Protection is associated with the child’s early life contact with farm animals, especially cows, as illustrated by our work in U.S. Amish and Hutterite farm children. These groups are similar in genetic ancestry and most asthma-associated lifestyles. However, Amish children, who are intensely exposed to cow barns in utero and throughout childhood, show low asthma risk, whereas Hutterite children, who live away from cow barns and are rarely exposed to them in early life, have a 4-fold higher disease prevalence. Asthma protection among the Amish is due to exposure to cow barns and barn-derived substances also present in Amish but not Hutterite house dust: administration of Amish but not Hutterite house dust extracts (DE) to mice was sufficient to suppress all cardinal phenotypes of allergic asthma. Protection by Amish DE requires innate immunity because it is abrogated in MyD88/Trif-deficient mice. Asthma risk is associated with allergic sensitization but also with early respiratory viral illnesses, especially those caused by RV. Therefore, asthma protection in Amish children may reflect the ability of Amish farm exposure to inhibit both allergic responses and viral illnesses, thus interfering with major asthma risk factors. We investigated whether Amish farm exposure protects against RV infection. Airway administration of Amish DE two days or even one month before RV infection strongly reduced viral infection readouts in mice. This suggested that natural agents in Amish DE induce both rapid and prolonged anti-viral responses. The latter likely represent trained immunity, an innate memory that relies on epigenetic programming. RV also elicited distinct responses in immune cells from farm-exposed (Amish) vs. unexposed (Hutterite) children. We hypothesize that exposure to Amish but not Hutterite farm dust activates innate pathways that rapidly protect against RV infection and enduringly train anti-RV responses through epigenetic priming at key loci in specific immune cell types. Leveraging a combination of mouse and human studies, we will characterize the mechanisms underlying rapid Amish DE-induced protection against RV infection (Aim 1) and prolonged training of anti-RV responses by Amish DE (Aim 2) in mice. Hutterite DEs will serve as controls in these Aims. Aim 3 will compare responses to RV in immune cells from farm-exposed (Amish) and unexposed (Hutterite) children to define transcriptional and epigenetic programs associated with protection. Because of the link between asthma and viral infections, deciphering the anti-viral properties of Amish farm exposure will potentially lead to effective asthma-protective strategies. Directly comparing the effects of Amish and Hutterite DEs on anti-viral responses will add specificity and significance to our results.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $806,740 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Allergy and Infectious Diseases Research	000	1	8/12/2026	NEW	$806,740
														Subtotal = $806,740

Grand Total All Awards = $806,740

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Anti-viral defense by natural microbial environmental agents

Award Number: R56AI201174

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/12/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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