Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults

Abstract

Importance: Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations.

Objective: To determine whether shorter telomeres in leukocytes, especially CD8CD28- T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults.

Design, setting, and participants: Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28-) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness.

Main outcome measures: Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness).

Results: Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC: odds ratio [OR] per 1-SD decrease in telomere length, 1.71 [95% CI, 1.08-2.72]; n = 128 [shortest tertile 77% infected; middle, 66%; longest, 57%]; CD4: OR, 1.76 [95% CI, 1.15-2.70]; n = 146 [shortest tertile 80% infected; middle, 71%; longest, 54%]; CD8CD28+: OR, 1.93 [95% CI, 1.21-3.09], n = 132 [shortest tertile 84% infected; middle, 64%; longest, 58%]; CD8CD28-: OR, 2.02 [95% CI, 1.29-3.16]; n = 144 [shortest tertile 77% infected; middle, 75%; longest, 50%]). CD8CD28- was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 [95% CI, 1.01-2.84]; n = 144 [shortest tertile, 26%; middle, 22%; longest, 13%]). The association between CD8CD28- telomere length and infection increased with age (CD8CD28- telomere length × age interaction, b = 0.09 [95% CI, 0.02-0.16], P = .01, n = 144).

Conclusion and relevance: In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28- T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.

Figure 1

Incidence of infection and colds by tertile of leukocyte telomere length. Ratio of telomere to single-copy gene amounts (T:S ratio) used as an index of average telomere length. Total Ns differ between cell types owing to insufficient DNA content in some blood samples. Data for each cell population are presented based on data from only those participants with complete telomere length data for that cell type. Y-axis segments in blue indicate range y = 0 to y = 30.

Figure 2

Association of CD8CD28− Telomere Length and Infection With Increasing Age. Ratio of telomere to single-copy gene amounts (T:S ratio) used as an index of average telomere length. Age is presented in tertiles in the figure to facilitate interpretation. Error bars indicate 95% CIs. Odds ratios (ORs) can be interpreted as the increase in the odds of infection with each 1-SD decrease in telomere length. Each age group was analyzed in a separate logistic regression analysis that included the following control variables: prechallenge viral-specific antibody titer, body mass index, age, race, sex/contraceptive use (men, women taking contraceptives, women not taking contraceptives), season of exposure, and days between blood draw for telomere assay and viral challenge. Conversion of ORs to relative risks (RRs) using the formula of Zhang & Yu and setting the infection rate for the unexposed group equal to that of the quartile of longest CD8CD28− telomere length (ie, 50%) yields RR, 0.75 (95% CI, 0.25–1.49) for 18- to 22-year-olds; RR, 1.65 (95% CI, 1.13–1.91) for 23- to 29-year-olds; and RR, 1.76 (95% CI, 1.21–2.04) for 30- to 55-year-olds.