[534] LIVER IRON LOAD AND HCV IN PATIENTS WITH BETA-THALASSEMIA MAJOR (B-TM): IMPACT OF CHELATION THERAPY ON SEVERITY OF LIVER DISEASE

Background and Aims: Sexual transmission of hepatitis C virus (HCV) is thought to rarely induce apparent disease and to be infrequent presumably because of low level of HCV virions in the semen. Recently however a case of sexual transmission of an acute resolving HCV infection has been documented with a bottlenecking effect on the evolution of the NS3 gene in the recipient suggesting that only a small number of infectious particles were transmitted (Quer 2005, J Virol. 79:15 13 1). HCV particles circulate in the blood of chronically infected patients as a very heterogeneous population of particles with very variable density. About 50% of virus circulate as very low density lipo-viro-particles (LVP) which are hybrid apoB containing lipoprotein-viral complexes (Andrt. 2002, J Virol. 76: 6919; Nielsen 2006, J Virol. 80: 2418). Studies in chimpanzee reported that low density plasma fractions were more infectious than higher density fractions (Bradley 1991, J Med Virol. 34: 206; Hijilcata 1993, J Virol 67: 1953). LVP genome quasispecies is a sub-population of the blood quasispecies and differs from the quasispecies of higher density particles (Deforges 2004, J Gen Virol. 8: 2515). We took advantage of the differential quasispecies distribution in the blood to determine from what density fraction the infectious particles were issued in this case of sexually HCV transmission. Methods: Plasma from the chronically infected man was collected 8 weeks before the transmission to his female sexual partner. Fractions of density and >1.055g/ml were prepared and NS3 gene from these fractions amplified, cloned and sequenced. Results: Complete sequences from 28 clones were analysed. Phylogenetic trees confirmed that quasispecies from low and high density particles differed. Significantly, the consensus sequence from the infected recipient segregated with one LVP cluster and was genetically closer to the LVP quasispecies than to higher density particle quasispecies. Conclusion: In agreement with previous studies showing that human plasma low density fractions were the most infectious for chimpanzee, these data provide evidence that LVP are also infectious for human. Results also indicate that LVP can be sexually transmitted. SEXUALLY TRANSMITTED