Dynamics of Persistent TT Virus Infection, as Determined in Patients Treated with Alpha Interferon for Concomitant Hepatitis C Virus Infection

Abstract

TT virus (TTV) is a recently identified widespread DNA virus of humans that produces persistent viremia in the absence of overt clinical manifestations. In an attempt to shed light on the dynamics of chronic infection, we measured the levels of TTV in the plasma of 25 persistently infected patients during the first 3 months of alpha interferon (IFN-␣) treatment for concomitant hepatitis C virus (HCV) infection. The first significant decline of TTV loads was observed at day 3 versus day 1 for HCV. Subsequently, the loads of TTV became progressively lower in most patients, but some initial responders relapsed before the end of the follow-up, suggesting that at least in some subjects the effects of IFN on TTV can be very short-lived. No correlation between the responses of TTV and HCV to therapy was found. Fitting the viremia data obtained during the first week of treatment into previously developed mathematical models showed that TTV sustains very active chronic infections, with over 90% of the virions in plasma cleared and replenished daily and a minimum of approximately 3.8 ؋ 10 10 virions generated per day. Low levels of TTV were occasionally detected in the peripheral blood mononuclear cells of patients who had cleared plasma viremia, thus corroborating previous results showing that these cells may support TTV replication and/or persistence.

TT virus infection: a novel virus-host relationship

“…Infection is characterised by persistent viraemia and the presence of replicating virus in a wide range of anotomical sites, including bone marrow, lymphoid tissue, lung and liver [6][7][8][9]. As an indication of its great replicative capacity in vivo, studies of the kinetics of clearance of viraemia during interferon-AE therapy have suggested that .10 10 TTV virions are produced every day, with 90% of the virus in plasma cleared and replenished over this period [10].…”

Isolation of Multiple TT Virus Genotypes from Spleen Biopsy Tissue from a Hodgkin's Disease Patient: Genome Reorganization and Diversity in the Hypervariable Region

“…These isolates differed by less than 2% in the remainder of their nucleotide sequences. An alignment of these isolates with 79 previously reported TT virus genotypes permits the proposal of TT virus genera and species within the family Anelloviridae in analogy to a previous proposal for the papillomaviruses (family Papillomaviridae).TT viruses (TTV) are ubiquitous in nature and have been demonstrated in more than 90% of serum samples from healthy individuals where they persist over time (14,16,27,41). Viral particles have been purified from feces (17, 34) and, in addition, are excreted in saliva, breast milk, and bile juice (9,38,47,49).…”

“…TT viruses (TTV) are ubiquitous in nature and have been demonstrated in more than 90% of serum samples from healthy individuals where they persist over time (14,16,27,41). Viral particles have been purified from feces (17, 34) and, in addition, are excreted in saliva, breast milk, and bile juice (9,38,47,49).…”

Human Circovirus TT Virus Genotype 6 Expresses Six Proteins following Transfection of a Full-Length Clone

“…They display over 30% nucleotide diversity (19) and are classified into five distantly related groups (13). TTVs are ubiquitous in nature and have been demonstrated in more than 90% of serum samples from healthy individuals, where they persist over time (5,10,12,16). A tissue culture system that supports efficient replication of TTV is not yet available (4,13), and this has delayed the study of both TTV genome replication and TTV gene expression.…”