Expression of Exogenous Human Hepatic Nuclear Factor-1α by a Lentiviral Vector and Its Interactions with Plasmodium Falciparum Subtilisin-like Protease 2

Overview

Journal Korean J Parasitol

Specialty Parasitology

Date 2012 Feb 23

PMID 22355214

Authors

Shunyao Liao

Yunqiang Liu

Bing Zheng

Pyo Yun Cho

Hyun Ok Song

Yun-Seok Lee

Suk-Yul Jung

Hyun Park

Affiliations

Soon will be listed here.

Abstract

The onset, severity, and ultimate outcome of malaria infection are influenced by parasite-expressed virulence factors as well as by individual host responses to these determinants. In both humans and mice, liver injury follows parasite entry, persisting to the erythrocytic stage in the case of infection with the fatal strain of Plasmodium falciparum. Hepatic nuclear factor (HNF)-1α is a master regulator of not only the liver damage and adaptive responses but also diverse metabolic functions. In this study, we analyzed the expression of host HNF-1α in relation to malaria infection and evaluated its interaction with the 5'-untranslated region of subtilisin-like protease 2 (subtilase, Sub2). Recombinant human HNF-1α expressed by a lentiviral vector (LV HNF-1α) was introduced into mice. Interestingly, differences in the activity of the 5'-untranslated region of the Pf-Sub2 promoter were detected in 293T cells, and LV HNF-1α was observed to influence promoter activity, suggesting that host HNF-1α interacts with the Sub2 gene.

References

Wykes M, Liu X, Beattie L, Stanisic D, Stacey K, Smyth M . Plasmodium strain determines dendritic cell function essential for survival from malaria. PLoS Pathog. 2007; 3(7):e96. PMC: 1904473. DOI: 10.1371/journal.ppat.0030096. View

Griffith J, OConnor C, Bernard K, Town T, Goldstein D, Bucala R . Toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host. J Infect Dis. 2007; 196(10):1553-64. DOI: 10.1086/522865. View

Soutoglou E, Papafotiou G, Katrakili N, Talianidis I . Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins. J Biol Chem. 2000; 275(17):12515-20. DOI: 10.1074/jbc.275.17.12515. View

Fortin A, Stevenson M, Gros P . Complex genetic control of susceptibility to malaria in mice. Genes Immun. 2002; 3(4):177-86. DOI: 10.1038/sj.gene.6363841. View

Myrick A, Munasinghe A, Patankar S, Wirth D . Mapping of the Plasmodium falciparum multidrug resistance gene 5'-upstream region, and evidence of induction of transcript levels by antimalarial drugs in chloroquine sensitive parasites. Mol Microbiol. 2003; 49(3):671-83. DOI: 10.1046/j.1365-2958.2003.03597.x. View

Crabb B, Cowman A . Characterization of promoters and stable transfection by homologous and nonhomologous recombination in Plasmodium falciparum. Proc Natl Acad Sci U S A. 1996; 93(14):7289-94. PMC: 38976. DOI: 10.1073/pnas.93.14.7289. View

Jain S, Li Y, Patil S, Kumar A . HNF-1alpha plays an important role in IL-6-induced expression of the human angiotensinogen gene. Am J Physiol Cell Physiol. 2007; 293(1):C401-10. DOI: 10.1152/ajpcell.00433.2006. View

Baxter E, Cummings W, Fournier R . Formation of a large, complex domain of histone hyperacetylation at human 14q32.1 requires the serpin locus control region. Nucleic Acids Res. 2005; 33(10):3313-22. PMC: 1143699. DOI: 10.1093/nar/gki645. View

Pace T, Olivieri A, Sanchez M, Albanesi V, Picci L, Kiamos I . Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage-specific expression. Mol Microbiol. 2006; 60(4):870-82. DOI: 10.1111/j.1365-2958.2006.05141.x. View

10.

Gunasekera A, Myrick A, Militello K, Sims J, Dong C, Gierahn T . Regulatory motifs uncovered among gene expression clusters in Plasmodium falciparum. Mol Biochem Parasitol. 2007; 153(1):19-30. DOI: 10.1016/j.molbiopara.2007.01.011. View

11.

Kooij T, Janse C, Waters A . Plasmodium post-genomics: better the bug you know?. Nat Rev Microbiol. 2006; 4(5):344-57. DOI: 10.1038/nrmicro1392. View

12.

Adachi K, Tsutsui H, Kashiwamura S, Seki E, Nakano H, Takeuchi O . Plasmodium berghei infection in mice induces liver injury by an IL-12- and toll-like receptor/myeloid differentiation factor 88-dependent mechanism. J Immunol. 2001; 167(10):5928-34. DOI: 10.4049/jimmunol.167.10.5928. View

13.

Lanzer M, Wertheimer S, de Bruin D, Ravetch J . Plasmodium: control of gene expression in malaria parasites. Exp Parasitol. 1993; 77(1):121-8. DOI: 10.1006/expr.1993.1068. View

14.

Rollini P, Fournier R . The HNF-4/HNF-1alpha transactivation cascade regulates gene activity and chromatin structure of the human serine protease inhibitor gene cluster at 14q32.1. Proc Natl Acad Sci U S A. 1999; 96(18):10308-13. PMC: 17884. DOI: 10.1073/pnas.96.18.10308. View

15.

Prudencio M, Rodriguez A, Mota M . The silent path to thousands of merozoites: the Plasmodium liver stage. Nat Rev Microbiol. 2006; 4(11):849-56. DOI: 10.1038/nrmicro1529. View

16.

Morosan S, Hez-Deroubaix S, Lunel F, Renia L, Giannini C, van Rooijen N . Liver-stage development of Plasmodium falciparum, in a humanized mouse model. J Infect Dis. 2006; 193(7):996-1004. DOI: 10.1086/500840. View

17.

Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez F, Talianidis I . Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev. 2006; 20(16):2293-305. PMC: 1553211. DOI: 10.1101/gad.390906. View

18.

Uzureau P, Barale J, Janse C, Waters A, Breton C . Gene targeting demonstrates that the Plasmodium berghei subtilisin PbSUB2 is essential for red cell invasion and reveals spontaneous genetic recombination events. Cell Microbiol. 2003; 6(1):65-78. DOI: 10.1046/j.1462-5822.2003.00343.x. View

19.

Carrolo M, Giordano S, Cabrita-Santos L, Corso S, Vigario A, Silva S . Hepatocyte growth factor and its receptor are required for malaria infection. Nat Med. 2003; 9(11):1363-9. DOI: 10.1038/nm947. View

20.

Yoshimoto T, Takahama Y, Wang C, Yoneto T, Waki S, Nariuchi H . A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection. J Immunol. 1998; 160(11):5500-5. View