Letizia Lanini

Human Metapneumovirus Associated with Respiratory Tract Infections in a 3-Year Study of Nasal Swabs from Infants in Italy

ABSTRACT The newly described human metapneumovirus (hMPV) is reported here to be more commonly associated with lower respiratory tract disease. The present study examined nasal swab specimens from 90 infants with acute respiratory tract infections in Pisa, Italy, over a period of three respiratory virus seasons. The incidence of infection varied in each of the 3 years, with the rates of positivity for hMPV being 7% in 2001 but 37 and 43% in 2000 and 2002, respectively. hMPV was noted to occur seasonally in a pattern typical of the frequency of occurrence of respiratory syncytial virus. More than one-half (14 of 23) of the infants infected with hMPV had bronchopneumonia. One-third (9 of 23) of the hMPV-infected patients were also infected with another respiratory virus, a relationship that has not previously been reported. Mixed infections did not account for a higher percentage of cases of bronchopneumonia than hMPV infection alone did. Furthermore, 7 of 17 infants whose plasma was also tested for hMPV RNA were demonstrated to have virus in both nasal swab and blood specimens. The study indicates that hMPV is seen as commonly as other respiratory viruses, may be associated with severe respiratory disease in infants, can establish mixed infections with other respiratory viruses, and has a seasonal occurrence.

TT virus loads and lymphocyte subpopulations in children with acute respiratory diseases

ABSTRACT TT virus (TTV) produces chronic plasma viremia in around 90% of healthy individuals of all ages and has, therefore, been proposed as a commensal human virus. We recently demonstrated that in children hospitalized for acute respiratory diseases high TTV loads were associated with severe forms of disease. Here, we report that in such children TTV loads showed an inverse correlation with the percentage of circulating total T and helper T cells and a direct correlation with the percentage of B cells. Thus, florid TTV replication might contribute to lymphocyte imbalances and, possibly, immunosuppressive effects, thus resembling related animal viruses.

Associations between Nasal Torquetenovirus Load and Spirometric Indices in Children with Asthma

Fifty-nine children with well-controlled, mild to moderate persistent asthma were studied for the presence and load of torquetenovirus (TTV) in nasal fluid. Rates of TTV positivity and mean nasal TTV loads were not dissimilar to those observed in the general population and in a group of 30 age- and residence-matched healthy control children without a history of asthmatic disease. However, in the children with asthma, 3 important indices of lung function--forced expiratory flow (FEF) in which 25% and 75% of forced vital capacity (FVC) is expired (FEF(25%-75%)), forced expiratory volume in 1 s/FVC, and FEF(25%-75%)/FVC--showed an inverse correlation with nasal TTV load. Furthermore, signs of reduced airflow were more frequent in the children with asthma who had high nasal TTV loads (> or =6 log(10) DNA copies/mL of nasal fluid) than they were in those who had low nasal TTV loads (<6 log(10) DNA copies/mL of nasal fluid), despite similar therapy regimens. In contrast, the control children showed no associations between nasal TTV load and the spirometric indices. Levels of eosinophil cationic protein in sputum were also greater in the children with asthma who had higher nasal viral burdens than they were in those who had lower nasal viral burdens. These findings are the first report of TTV infection status in children with asthma and suggest that TTV might be a contributing factor in the lung impairment caused by this condition.

Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried.

ABSTRACT In 239 torquetenovirus-positive people, multiple-genogroup infections were common and associated with higher viral loads than would be expected from simple additive effects. The latter observation was restricted to the infections which included both genogroups 1 and 3, pointing to the possible existence of some kind of infection facilitation between these genogroups.

Torquetenovirus DNA drives proinflammatory cytokines production and secretion by immune cells via toll-like receptor 9

Active infection with torquetenovirus (TTV) has been associated with an increased severity of diseases in which inflammation plays a particularly important pathogenetic role. Here, we report that cloned DNA of a genogroup 4 TTV (ViPiSAL) is an activator of proinflammatory cytokine production by murine spleen cells and that the effect is mediated via toll-like receptor (TLR)9. The same DNA also increased the levels of proinflammatory cytokines induced by two well-characterized TLR9 stimulants. Finally, in silico analyses of the genomes of ViPiSAL and other TTVs revealed marked differences in the representation of CpG motifs known to be most effective at activating immune cells via TLR9. These findings demonstrate for the first time that at least one TTV isolate has the potential to stimulate and co-stimulate inflammatory responses.

Role of Hematopoietic Cells in the Maintenance of Chronic Human Torquetenovirus Plasma Viremia

ABSTRACT Many aspects of the life cycle of torquetenoviruses (TTVs) are essentially unexplored. In particular, it is still a matter of speculation which cell type(s) replicates the viruses and maintains the generally high viral loads found in the blood of infected hosts. In this study, we sequentially measured the TTV loads in the plasma of four TTV-positive leukemia patients who were strongly myelosuppressed and then transplanted with haploidentical hematopoietic stem cells. The findings provide clear quantitative evidence for an extremely important role of hematopoietic cells in the maintenance of TTV viremia.

Torque Teno Virus Viremia Load Size in Patients with Selected Congenital Defects of Innate Immunity

ABSTRACT Plasma loads of torque teno virus (TTV) among individuals differ extensively beginning early in life, suggesting a role for innate immunity. Here, congenital mannose-binding lectin deficiencies, but not deficiencies in respiratory ciliary function, correlated with increased TTV loads. Notably, however, the presence of either disorder was associated with particularly high TTV loads.

Correlation between Torque Tenovirus Infection and Serum Levels of Eosinophil Cationic Protein in Children Hospitalized for Acute Respiratory Diseases

Children with bronchopneumonia have considerably higher Torque tenovirus (TTV) loads than do children with milder acute respiratory diseases (ARDs). Moreover, in children with ARDs, high TTV loads correlate with low percentages of circulating CD3+ and CD4+ T cells and with elevated percentages of B cells, suggesting that TTV might be immunomodulatory. Here, we show that, in children with ARDs, the presence of TTV and TTV load correlate with concentrations of serum eosinophil cationic protein. The possible mechanisms whereby TTV infection might lead to augmented activity of eosinophils and the implications for pathogenesis are discussed.

Rapid Increase in Total Torquetenovirus (TTV) Plasma Viremia Load Reveals an Apparently Transient Superinfection by a TTV of a Novel Group 2 Genotype

ABSTRACT An apparently transient infection by a superimposed torquetenovirus (TTV) in a subject who already carried three different genotypes of the virus is described. The superinfection induced a rapid increase in the plasma TTV load and a decline in immunocomplexed virus. The superinfecting TTV was a novel group 2 genotype.

WU and KI Polyomaviruses Remain Orphans in Adults

To the Editor—We read with interest the brief report by Barzon et al [1] showing that WU and KI polyomaviruses (WUPyV and KIPyV) reactivate and are frequently detectable in the brains of human immunodeficiency virus (HIV)–positive patients without being associated with progressive multifocal leukoencephalopathy. We also recently disproved such an association between novel polyomaviruses (including lymphotropic polyomavirus [LPyV] and Merkel cell carcinoma polyomavirus [MCPyV]) and progressive multifocal leukoencephalopathy in HIV-negative patients [2]. However, because the prevalence of novel polyomaviruses remains high and because they have been shown to reactivate under conditions of immune deficiency [3], they could still prove to be useful as surrogate markers of functional immunodeficiency, as was recently proposed for another orphan virus, torquetenovirus (TTV) [4]. Therefore, we analyzed the occurrence of WUPyV, KIPyV, LPyV, and MCPyV viremia (by the same methods used previously [3]) at the time of peak TTV viremia after high-dose chemotherapy supported by autologous stem cell transplant in 17 patients with multiple myeloma, 1 with non-Hodgkin lymphoma, and 1 with systemic sclerosis. All samples tested negative. It remains difficult to identify the body site with the highest prevalence and, hence, the greatest sensitivity for these viruses; it could be feces [5], in contrast to urine for JC and BK polyomaviruses [6]. Given that many polyomaviruses are lymphotropic and retain oncogenic potential, we investigated their occurrence in lymph node biopsy samples from patients with lymphoma or leukemia. We could not find any occurrence of WUPyV, KIPyV, LPyV, and MCPyV in any of 49 lymph node samples tested (from, namely, 11 patients with follicular lymphoma, 14 with diffuse large B cell lymphoma, 10 with B cell chronic lymphocytic leukemia, 7 with Hodgkin lymphoma, 2 with hairy cell leukemia, 2 with mantle cell lymphoma, 1 with Burkitt lymphoma, 1 with splenic marginal zone lymphoma, and 1 with B cell acute lymphoblastic leukemia).