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Lentiviral Vector Systems for Gene Transfer (Medical by Gary L. Buchschacher Jr.

By Gary L. Buchschacher Jr.

The human immunodeficiency viruses (HIVs), particularly HIV-1, are the causative agent accountable for the present around the world epidemic of received immunodeficiency syndrome (AIDS). an incredible attempt has therefore been underway during the last 20 years to appreciate and keep an eye on this pathogen. in this time, an immense wisdom base has gathered concerning the function of viral components within the HIV-1 lifestyles cycle, and the interplay of HIV-1 with the host telephone is changing into more and more understood. definite positive factors of HIV, for instance its skill to contaminate non-dividing cells, are being exploited within the improvement of novel gene treatment automobiles. This quantity offers an summary of the present information about the HIV replication cycle and should function an advent to next chapters that tackle particular features of lentiviral-based gene treatment.

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It is currently unclear to what extent RNA dimerization is required for efficient encapsidation. The specific encapsidation of retroviral RNAs into virus particles is mediated by interactions between the packaging signal and the NC domain of Gag. Nearly all retroviral NC proteins contain one or two zinc finger motifs, each of which coordinates a zinc ion. HIV-1 NC contains two zinc-finger motifs (Fig. 7) of the “CCHC” type (Cys-X2-Cys-X4-His-X4-Cys; where X denotes a variable amino acid). The zinc fingers of HIV-1 NC are flanked by highly basic sequences.

This topic will be the focus of Chapter 3. References 1. Freed EO, Martin MA. HIVs and their replication. In: Knipe DM, Howley PM, Griffin D, Lamb RA, Roizman B, Martin MA, Straus SE, eds. Fields Virology, 4th ed. Philadelphia: Lippincott, Williams, and Wilkins, 2001:1971-2041. 2. Bour S, Geleziunas R, Wainberg MA. The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection. Microbiol Rev 1995; 59:63-93. 3. Kwong PD, Wyatt R, Robinson J et al.

Nature 1996; 381:744-745. 53. Vogt VM. Ubiquitin in retrovirus assembly: Actor or bystander? Proc Natl Acad Sci USA 2000; 97:12945-12947. 54. Wlodawer A, Erickson JW. Structure-based inhibitors of HIV-1 protease. Annu Rev Biochem 1993; 62:543-585. 55. Yeager M, Wilson-Kubalek EM, Weiner SG et al. Supramolecular organization of immature and mature murine leukemia virus revealed by electron cryo-microscopy: Implications for retroviral assembly mechanisms. Proc Natl Acad Sci U S A 1998; 95:7299-7304.

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