The xenotropic murine leukemia virus-related virus (XMRV) has been recently linked to chronic fatigue syndrome in a US cohort in whom the virus was demonstrated in 67% patients vs 3.7% healthy controls. Albeit this finding was not substantiated by subsequent reports and eventually considered a laboratory contamination, the matter is still the object of intense debate and scrutiny in various cohorts of patients. In this work we examined well-clinically characterized Italian patients affected by chronic fatigue syndrome, and also fibromyalgia and rheumatoid arthritis, two chronic illnesses of basically unknown etiology which show quite a few symptoms in common with chronic fatigue syndrome. Although we used recently updated procedures and controls, the XMRV was not found in 65 patients with chronic fatigue syndrome diagnosis, 55 with fibromyalgia, 25 with rheumatoid arthritis, nor in 25 healthy controls. These results add to the ever-growing number of surveys reporting the absence of XMRV in chronic fatigue syndrome patients and suggest that the virus is also absent in fibromyalgia and rheumatoid arthritis.

The human pathogen xenotropic murine leukaemia virus-related virus (XMRV) has been tentatively associated with prostate cancer and chronic fatigue syndrome. Unfortunately, subsequent studies failed to identify the virus in various clinical settings. To determine whether XMRV circulates in humans and the relationship with its host, we searched for the virus in 124 human immunodeficiency virus-infected patients who might have been exposed to XMRV, might be prone to infection as a result of progressive immunodeficiency, and had not yet been treated with antiretroviral drugs. Using nested PCR and single-step TaqMan real-time PCR, both designed on the XMRV gag gene, we could not find any positive samples. These findings add to the growing amount of scepticism regarding XMRV.

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.

Torque Teno virus (TTV) has been demonstrated to be present persistently in the blood of healthy individuals without evidence that it causes any disease process. The levels of TTV vary in patients co‐infected with other viruses and there has been considerable speculation as to whether TTV contributes to pathogenesis by other viruses or if the varying levels might be related to immune activation in the host. In the present study, the load of TTV was examined in plasma and peripheral blood mononuclear cells (PBMCs) following immunization of subjects with either influenza (a recall antigen) or hepatitis B virus (HBV) (a new antigenic exposure). The results overall did not indicate a significant change in TTV titers over a 90 day observation period; however, when TTV genogroup was taken into consideration there was an increase in viral load in plasma at some time points for subjects persistently infected with genogroup 3. While this was observed in both influenza and HBV immunized subjects, the effect was more profound in HBV vaccination. Thus, it appears that exposure to a new antigen rather than a recall antigen may stimulate TTV replication more effectively. The data further suggest that investigating the interactions between TTV and its host might require to examine specifically each TTV genogroup separately in order to determine if certain TTV types have any role in disease pathogenesis. J. Med. Virol. 75:358–365, 2005. © 2004 Wiley‐Liss, Inc.

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.

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 (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.

Blood and gastric tissue biopsies of 34 patients with gastritis were tested for the presence of TT virus (TTV), a ubiquitous virus found in the blood of most humans. Thirty-one of these patients were TTV positive, and 27 patients had virus in both tissues. In addition, 13 of the patients who had TTV in gastric tissue were Helicobacter pylori positive. There was an association of higher TTV titers in gastric tissues of patients who were H. pylori positive than in those in whom the bacterium could not be detected. Furthermore, this association was stronger in H. pylori-positive patients with the presence of the cagA protein. Of 10 specimens in which genogroup determination was carried out in the gastric corpus, 5/5 that were H. pylori positive showed the presence of TTV genogroup 3, while for those that were H. pylori negative, 5/5 showed the presence of genogroup 1t. By contrast, genogroup 1 was found in the corpus of only one H. pylori-positive patient, and genogroup 3 in only one H. pylori-negative patient. The histological severity of gastritis did correlate significantly with loads in the gastric tissues. There was no significant difference in TTV titer in blood of patients regardless of H. pylori infection status. These findings pique interest in clarifying the role of TTV, alone or in association with H. pylori infection, in the pathogenesis of gastritis.

A group of 24 well-characterized patients doubly infected with hepatitis C virus (HCV) and TT virus (TTV) were studied to evaluate whether the loads and number or identity of the genogroups of TTV they carried could affect the response of HCV infection to interferon-alpha (IFN) treatment. The features of HCV infection in the study patients provided a fair representation of the variables that are usually found in considering patients for IFN treatment. The same was true for the features of TTV infection. In particular, plasma loads of TTV varied over a wide range in individual patients, and infection with multiple TTV genogroups was extremely frequent. TTV genogroups 1 and 3 were the most prevalent, followed by genogroups 4 and 5. The HCV response to IFN was evaluated by measuring plasma viraemia at 24 hours and 30 days after initiation of treatment. The results showed that the TTV parameters investigated had little or no impact on the response of HCV to therapy. Due to study design, these results do not exclude that the presence of a concomitant TTV infection can affect how HCV infection responds to treatment. However, they indicate that, should such effects exist, they would be independent on load and genetic features of the infecting TTV.