Human torque teno virus (TTV) was first discovered in a Japanese patient with acute post-transfusion hepatitis in 1997 . It is a small and non-enveloped virus, with the size of 30 nm diameter, which carries an approximately 3.8 kb, circular negative sense, single-stranded DNA genome [2, 3]. According to the latest International Committee on Taxonomy of Viruses (ICTV) classification [4, 5], TTV has been classified into the Anelloviridae family which includes also torque teno mini virus (TTMV), formerly known as TTV-like Mini virus (TLMV), and TT midi virus (TTMDV), discovered in 2000 and 2007 respectively [6, 7]. The Anelloviridae family contains 11 genera and TTMV belongs to the genus Betatorquevirus, where the TTV and TTMDV are in Alphatorquevirus and Gammatorquevirus genera respectively [4, 5]. All these viruses have similar genome structure but different genome sizes: 3.7-3.8 kb for TTV, 3.2 kb for TTMDV and 2.8-2.9 for TTMV [6–9].
Using alternative splicing, TTV generates three mRNA species and produces at least six proteins by alternative translation initiation . TTV ORF1 is the largest ORF and encodes a capsid protein, which has an arginine-rich N terminus that is suggested to have DNA binding activity and to function in packaging of the viral DNA [3, 11, 12]. The noncoding region, highly conserved among TTVs , has a very high GC content and is around 170 bp in size. TTVs are widely spread in the whole human population and most people carry a TTV or TTMV infection but the association of TTV with disease is unclear [14–16]. Moreover, the immunological properties, the possible pathogenic role and other aspects of TTVs are still poorly understood. Persistent infection and co-infection with several genotypes are common [17–19], and some investigations suggest that TTVs are associated with hepatitis, gastritis, cancer, and acute respiratory diseases (see below), but no clear evidence has ever been presented. TTV-like sequences were identified in tumors of the gastrointestinal tract and myelomas . Furthermore, several studies have mentioned the possible association of TTV with respiratory disease, asthma and its role in prognosis of idiopathic pulmonary fibrosis [21–25], while others suggested a possible association of TTV with aplastic anemia, childhood leukemia, and lymphomas [26–28]. It is also possible that the viral load, co-infections with multiple types or other agents, the immune status of the host, differences in genomic sequence or more of these factors at the same time have an influence on the pathogenicity . TTVs reveal a remarkable heterogeneity and multiple genotypes have already been described . It is possible that only some genotypes of TTV have a capacity to cause disease or are characterized by a higher pathogenicity than others . Therefore, to have a comprehensive view on TTVs and consider their possible roles in human infections, identification of all genotypes is needed, as it represents the first step towards understanding the epidemiology, the immunology, the pathogenesis and other aspects of this virus family. In this study we describe a new genotype of TTMV identified in serum of two HIV-1 positive patients, which we tentatively named TTMV-13.