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Early-life human cytomegalovirus infections in Canadians : implications for a healthy development

University of British Columbia

Background: Cytomegalovirus (CMV) is a ubiquitous herpesvirus that has evolved with humans over millions of years and causes lifelong infection. Therefore, CMV is considered part of the “virome”, the viral component of the human microbiome. The bacterial intestinal microbiome is essential for the education of the immune system and appears to be critical for immunologic health, however, much less is known about the importance of the virome on healthy development. CMV has potent immunomodulatory effects and can replicate within the intestines. Thus, CMV might impact the composition of the bacterial intestinal microbiome and its relationship with the developing immune system. CMV infections are occurring later in life in high income countries like Canada, which also have a high prevalence of allergic diseases. Indeed, CMV could be a necessary component of the virome to educate the immune system and prevent the later development of allergic diseases, such as asthma and eczema. Thus, we hypothesized that infection with CMV in healthy Canadian infants impacts the composition of the intestinal microbiome and protects against the development of allergic diseases. Methods: Urine samples collected from CHILD Study participants at 3 and 12 months of age were tested for CMV by qPCR. The CHILD Study questionnaire, fecal 16S rRNA sequence and clinical diagnoses data were used to determine risk factors for infection, CMV impact on the microbiome and CMV associations with allergic diseases, respectively. Results: Of the 1,151 Canadian children tested, 19% were infected by 1 year of age. The duration of breastfeeding and parental ethnicity was associated with the risk of infant CMV infection. CMV infection by 3 months of age was associated with a significantly decreased α-diversity and altered β-diversity of the intestinal microbiome. CMV infection was not associated with a clinical diagnosis of asthma or eczema but was associated with a higher risk of an atopic phenotype at 1 year of age. Significance: This study provides the first evidence that early-life CMV infection influences the diversity of the intestinal microbiome. Additionally, it provides supportive evidence that elimination of CMV infection through vaccination is unlikely to contribute to allergic disease development.

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2019-04-08

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/69534

Pathology and Laboratory Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/