Antigenic diversity and seroprevalences of Torque teno viruses in children and adults by ORF2-based immunoassays

Abstract

Torque teno viruses (TTVs) circulate widely among humans, causing persistent viraemia in healthy individuals. Numerous TTV isolates with high genetic variability have been identified and segregated into 29 species of five major phylogenetic groups. To date, the diversity of TTV sequences, challenges in protein expression and the subsequent lack of serological assays have hampered TTV seroprevalence studies. Moreover, the antigenic relationships of different TTVs and their specific seroprevalences in humans remain unknown. For five TTV strains -belonging to different species of four genogroups -we developed, using recombinant glutathione Stransferase (GST)-fused TTV ORF2 proteins, glutathione-GST capture enzyme immunoassays (EIAs) detecting antibodies towards conformational epitopes. We then analysed serum samples from 178 healthy adults and 108 children; IgG reactivities were observed either towards a single strain or towards multiple strains, which pointed to antigenic distinction of TTV species. The overall seroprevalence for the five TTVs peaked at 43 % (18 of 42) in children 2-4 years of age, subsequently declined, and again reached 42 % (74 of 178) among adults. TTV6 species-specific IgG predominated in children, whereas that for TTV13 predominated in adults. During a 3 year follow-up of the same children, both species-specific seroconversions and seroreversions occurred. This is the first EIA-based study of different TTVs, providing a new approach for seroepidemiology and diagnosis of TTV infections. Our data suggest that different TTVs in humans may differ in antiviral antibody profiles, infection patterns and epidemiology.

Local Virus Extinctions following a Host Population Bottleneck

“…Anelloviruses are under immunological control, since induced or inborn immunodeficiency is associated with increases in viral loads (59)(60)(61)(62)(63). The rates of seroreactivity were shown to increase rapidly in infants (64), and infection is believed to be generally chronic. Anelloviruses have been reported in many tissues and bodily fluids, including respiratory fluids, blood, breast milk, cervical secretions, semen, urine, and feces (65)(66)(67)(68)(69)(70)(71)(72)(73).…”

Expression of TTV-ORF2 Protein for Detection of Anti-TTV IgG Antibodies in Human Sera

“…As discussed earlier, ORF2 region encodes a protein of near about 20 KDa [8] which is a non-structural protein and has been reported to induce host immune response against TTV [8,[34][35][36]. Although, earlier attempts in several studies focused on the expression of N22 region [26] and ORF1 [28,37], however, their protein product could not prove successful antigenic agent to induce host immune response or for their use in developing immunoassays for sero-detection of TTV infection.…”

Development of an Immunoassay for Detection of Torque Teno Virus (TTV) Antibodies Using the N22 Expression Product from TTV Genotype 2

“…Although similar attempts were made in the past using various subgenomic regions of TTV-DNA, including ORF-1 [40,43,44] and ORF-2 [15,28,32]; however, we envisaged that N22, being a conserved region, could be a better subgenomic region for use in the development of immunoassay. Furthermore, all of the studies reported so far are based on genotype 1 since it is highly prevalent globally.…”

“…Earlier studies have demonstrated that different genetic variants are antigenically distinct. However, it is not clear whether these variants have some biological or pathogenic differences also [15]. Of course, few recent reports point to an association between genotypes/genogroups and the type of disease caused [17,18].…”

“…Whereas genogroups 1 and 3 are the most common globally, genogroup 2 is detected quite rarely [15]. Persistent infections and coinfections with multiple genotypes/ genogroups are noted frequently [16].…”