TT virus in the nasal secretions of children with acute respiratory diseases: relations to viremia and disease severity

Abstract

The natural history and pathogenic potential of the recently identified TT virus (TTV) are currently a matter of intensive investigation. In an attempt to shed some light on these issues, nasal and blood specimens of 1- to 24-month-old children hospitalized with a clinical diagnosis of acute respiratory disease (ARD) were examined for the presence, load, and genetic characteristics of TTV. The results have indicated that at least in young children, the respiratory tract not only represents a route by which abundant TTV can be shed into the environment but also may be a site of primary infection and continual replication. Although we found no compelling evidence that TTV was the direct cause of ARD in some of the children studied, the average loads of TTV were considerably higher in patients with bronchopneumonia (BP) than in those with milder ARD, raising interesting questions about the pathophysiological significance of TTV at this site. Furthermore, group 4 TTV was detected almost exclusively in children with BP.

FIG. 1.

TTV loads in paired nasal and blood samples from the 18 children in the pilot study that were found virus positive in both specimens. •, TTV DNA copy numbers in nasal fluid versus plasma; ○, TTV DNA copy numbers in total DNA from nasal cells versus PBMC. Broken lines connect the data for each individual patient. Most points lie above the diagonal line, indicating higher loads in nasal samples than in blood samples.

FIG. 2.

Phylogenetic analysis of 27 TTV isolates from the pilot study. (A) Tree based on the 151-bp ORF1 segment amplified by the group 1-specific PCR. (B) Tree based on the 214-bp ORF1 segment amplified by the group 3-specific PCR. Both segments had primer nucleotides subtracted. Nasal (▪) and plasma (•) isolates from the present study are in boldface type. GenBank sequences are indicated by the isolate name. The PMV isolate was used as the outgroup. Bootstrap values above 67% of 1,000 replicates are shown at branch points, to show the significance of the grouping. Bars represent the number of nucleotide substitutions per site. Bars with numbers to the right of each tree indicate the TTV genotypes within which the sequences identified in this study clustered (the others are omitted for simplicity).

FIG. 3.

TTV loads in the 151 plasma and 100 nasal fluid specimens from children with ARD, subdivided by respiratory disease (BP versus other ARD). (A) Thick and thin lines represent nasal fluid and plasma samples, respectively. Most steps represent single patients. TTV loads in nasal fluid and plasma differed significantly between patients with BP and other ARD at P < 0.00001 and at P < 0.00001, respectively (Wilcoxon test). (B) Results stratified based on the TTV load in plasma (dotted line) and nasal fluid (continuous line). Each point represents the ratio between the number of patients with BP and the number of patients with other ARD. The numbers in parentheses are the number of patients with BP/the number of patients with other ARD.