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bioRxiv2023

Integrated Drivers of Basal and Acute Immunity in Diverse Human Populations

Prior studies have identified genetic, infectious, and biological associations with immune competence and disease severity; however, there have been few integrative analyses of these factors and study populations are often limited in demographic diversity. Utilizing samples from 1,705 individuals in 5 countries, we examined putative determinants of immunity, including: single nucleotide polymorphisms, ancestry informative markers, herpesvirus status, age, and sex. In healthy subjects, we found significant differences in cytokine levels, leukocyte phenotypes, and gene expression. Transcriptional responses also varied by cohort, and the most significant determinant was ancestry. In influenza infected subjects, we found two disease severity immunophenotypes, largely driven by age. Additionally, cytokine regression models show each determinant differentially contributes to acute immune variation, with unique and interactive, location-specific herpesvirus effects. These results provide novel insight into the scope of immune heterogeneity across diverse populations, the integrative effects of factors which drive it, and the consequences for illness outcomes.

immunology↗

bioRxiv2019

Effect of geographic isolation on the nasal virome of indigenous children

The influence of living in small remote villages on the diversity of viruses in the nasal mucosa was investigated in three Colombian villages with increasing levels of geographic isolation. Viral metagenomics was used to characterize viral nucleic acids on nasal swabs of 63 apparently healthy young children. Sequences from human virus members of the families Anelloviridae, Papillomaviridae, Picornaviridae, Herpesviridae, Polyomaviridae, Adenoviridae, and Paramyxoviridae were detected in a decreasing fraction of children. The diversity of human viruses was not reduced in the most isolated indigenous Kogi villages. Multiple viral transmission clusters were also identified as closely related variants of rhinoviruses A or B in 2 to 4 children from each of villages. The number of papillomavirus detected was greater in the village most exposed to outside contacts while conversely more anellovirus infections were detected in the more isolated indigenous villages. Genomes of viruses not known to infect humans, including in the family Parvoviridae (genus densoviruses), Partitiviridae, Dicistroviridae, and Iflaviridae and circular Rep expressing ssDNA genomes (CRESS-DNA) were also detected in nasal swabs likely reflecting environmental contamination from insect, fungal, and unknown sources. Despite the high level of geographic and cultural isolation, the diversity of human viruses in the nasal passages of children was not reduced in indigenous villages indicating ongoing exposure to globally circulating viruses.\n\nImportanceExtreme geographic and cultural isolation can still be found in some indigenous South American villages. Such isolation may be expected to limit the introduction of globally circulating viruses. Very small population size may also result in rapid local viral extinction due to lack of sufficient sero-negative subjects to maintain transmission chains of rapidly cleared viruses. We compared the viruses in the nasal passage of young children in three villages with increasing level of isolation. We find that isolation did not reduce the diversity of viral infections in the most isolated villages. Ongoing viral transmission of rhinoviruses could also be detected within all villages. We conclude that despite their geographic isolation remote villages are continuously exposed to globally circulating respiratory viruses.

epidemiology↗