TT Virus Infection Among Individuals At-Risk for Hepatitis C Virus and Human Immunodeficiency Virus Type 1 in Vietnam

             Pursuit of the infectious cause of chronic hepatitis among individuals with non-A to G hepatitis has led to the discovery of a circular, single-stranded DNA virus, designated TT virus (TTV), which, based on viral sequence analysis, belongs to a new virus family.  The principal modes of transmission of TTV are poorly understood, and to what extent individuals with HIV-1 infection are at risk of TTV infection is unclear.  To address this issue, we determined if injection drug use (IDU) and high-risk heterosexual activity (HRHA), principal modes of acquiring HIV-1 infection, place individuals at greater risk of acquiring TTV.  DNA, extracted from sera or filter paper-blotted whole blood, obtained during August 1997 and June 1998 from 324 Vietnamese (148 men and 176 women), were analyzed for TTV sequences by hot-start, hemi-nested PCR.  Prevalence of TTV viremia was similar among individuals engaging in IDU or HRHA (23.4% vs. 20.2%; P > 0.5), with no age- or gender-specific differences.  No association was found between TTV viremia and coinfection with HIV-1 or HCV.  Phylogenetic analysis of 30 TTV sequences revealed two distinct genotypes and four subtypes, which did not segregate according to gender, HIV-1 and HCV risk behaviors or geographic residence.  Among HIV-1- or HCV-infected Vietnamese, who presumably acquired their infection by either the parenteral or non-parenteral route, our data indicate no clear association between acquisition of TTV infection and risk behavior for HIV-1 or HCV infection, suggesting that the usual route of TTV transmission in Vietnam is other than parenteral or sexual.

Figure 1. Representative phylogenetic tree, constructed by the CLUSTAL W program, using the neighbor-joining method.  The tree is based on the 238-bp open reading frame 1 of TTV genome.  TTV strains from Vietnam are designated with the prefix VI.  The phylogenetic positions of TTV subtype 1a from Japan (N22 - AB017767}, CS4,4 TA278 - AB008394), China (Ch1 - AF055897) and Thailand (TTV3 - AF078114}); subtype 1b from Japan (TX011 - AB017769, CS5,4 G102001 - AB011488); subtype 2 from Japan (NA004 - AB017771 and TS003 - AB017770) are shown.  Branch lengths are drawn in proportion to the number of nucleotide substitutions per site, and bootstrap probabilities (1,000 iterations) exceeding 80% for each node are noted in italics.  GenBank accession numbers for Vietnam TTV strains are: AF133540 to AF133567.

Nerurkar, V.R., Woodward, C.L., Nguyen, H.T., Miller, F.D., Tashima, L.T., Zalles-Ganley, A., Chua, P.K., Peterson, J.E., Chi, P.K., Long, H.T., Detels, R., and Yanagihara, R.:  Lack of association between a recently described post-transfusion hepatitis-related DNA virus, TT virus, among individuals at-risk for hepatitis C virus and human immunodeficiency virus type 1 in Vietnam. International Journal of Infectious Diseases (in press).

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