Intra-host GI.1 norovirus evolution is shaped by genetic drift and purifying selection.

Area of Science:

• Virology
• Evolutionary Biology
• Immunology

Background:

• Human noroviruses exhibit significant genetic diversity with over 30 genotypes known.
• Understanding the origins and shaping of norovirus genetic diversity remains incomplete.
• Intra-host evolution and its drivers in human norovirus infections require further investigation.

Purpose of the Study:

• To investigate the origins of human norovirus genetic diversity.
• To analyze intra-host norovirus evolution in experimentally infected individuals.
• To determine the impact of host antibody responses on viral evolution.

Main Methods:

• Analysis of intra-host norovirus evolution using Norwalk virus (GI.1[P1]) experimental infection.
• Investigation of viral dynamics, antibody response impact, and inoculum-to-host evolution.
• Assessment of intra-host mutations for evidence of global circulation and structural distribution.

Main Results:

• Most detected intra-host mutations arose de novo within individuals and were not present in the inoculum.
• The majority of intra-host mutations were detected only once during shedding and did not circulate globally.
• No significant difference in mutation distribution was observed between individuals with or without positive antibody responses.

Conclusions:

• Stochastic processes, rather than host immune pressure, primarily govern intra-host viral diversity in acute norovirus infections.
• Strong fitness constraints purify the majority of mutations during infection.
• Further research into structural, chemical, and fitness constraints is needed to fully understand norovirus evolution.