Recent discoveries have highlighted the influence of host genomics on hepatitis C virus (HCV) infection outcomes. As a result, our views on hepatitis C pathogenesis and therapeutic approaches have been transformed. The recognition of the impact of single-nucleotide polymorphisms (SNPs) of the genes interleukin 28B (IL28B), inosine triphosphatase (ITPA) and low-density lipoprotein cholesterol re...

Ribavirin remains an important component of hepatitis C treatment in certain clinical scenarios, but it causes hemolytic anemia. A quantitative understanding of the ribavirin exposure-anemia relationship is important in dose individualization/optimization. We developed a model relating ribavirin triphosphate (RTP) exposure in red blood cells (RBCs), RBC lifespan, feedback regulation of RBC prod...

Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results i...

Tumor Immunotherapeutic Gels In article number 2204273, Dunfang Zhang, Hang Zhao, and co-workers demonstrate that an inosine-based supramolecular hydrogel, IPBisoG, can achieve the gradual sequential release of inosine aPDL1. Inosine, which enhancs proliferation function CD8+ T cells, together with aPDL1, blocker immunosuppressive pathway in tumor microenvironment, could highly enhance vivo eff...

The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seroposit...

The structure of human inosine triphosphate pyrophosphohydrolase (ITPA) has been determined using diffraction data to 1.6 A resolution. ITPA contributes to the accurate replication of DNA by cleansing cellular dNTP pools of mutagenic nucleotide purine analogs such as dITP or dXTP. A similar high-resolution unpublished structure has been deposited in the Protein Data Bank from a monoclinic and p...

LOK concentrations of p-chloromercuribenzoate (PCMB), Zn++, or Cd++ increase the ATPase and CTPase activities of myosin B but inhibit ITPase and GTPase activities. Higher concentrations of these modifiers inhibit the activit,ics of all the IIIIcleoside triphosphat,es (NTP). Dialysis against cysteine ethyl ester (CEE) increases t,he ATPase and CTPase activit,ies of myosin but decreases the ITPas...

Combination therapy of pegylated interferonwith ribavirin (PEG-IFN/RBV) is a standard of care for chronic hepatitis C (CHC). The majority of CHC patients are infected with HCV genotype I. The recent discovery revealed by a genome-wide association study technology provides the important role of interleukin-28B (IL28B) and inosine triphosphatase (ITPA) in HCV infection. In addition, response to P...