Retroviral reverse transcriptases (other than those of HIV-1 and murine leukemia virus): A comparison of their molecular and biochemical properties
Introduction
This chapter describes the reverse transcriptases (RTs) of retroviruses, other than those of human immunodeficiency virus type 1 (HIV-1) and murine leukemia virus (MLV) that are covered in detail in other chapters of this special issue devoted to reverse transcriptases. Previous reviews on retroviral RTs have been published since their discovery in the late 1960s and early 1970s (Verma, 1977, Gerard and Grandgenett, 1980, Skalka and Goff, 1993, Telesnitsky and Goff, 1997). These reviews have underscored the pivotal historic contributions of various studies to our understanding of the world of reverse transcription as well as the biochemistry of the RTs. In this chapter, we will briefly describe this earlier research, while emphasizing the more recent studies performed on RTs.
The first basic studies on retroviral RTs were performed on RTs purified from avian sarcoma and leukosis virions (ASLV). Additional studies have been described later on with recombinant RTs, as they could be more easily obtained, purified, genetically manipulated and tested. The different RTs discussed in the chapter were divided into five different groups according to the most recent taxonomy of the retroviruses from which they are derived: the alpharetroviruses, lentiviruses (other than HIV-1), betaretroviruses, deltaretroviruses (all of them are orthoretroviruses) and the spumaretroviruses. The MLV RT, a prototype of the RTs of gammaretroviruses is discussed in another paper in this special issue on retroviral reverse transcription (Coté and Roth, 2008). Each RT group is described herein in the following sections.
Section snippets
Alpharetroviruses (ASLV)
Initial studies of the RT enzyme were done with material prepared from virions of alpharetroviruses. Large quantities of avian myeloblastosis virus (AMV) could be prepared relatively inexpensively from plasma of infected chickens. Alternatively, cultured cells infected with avian sarcoma viruses (ASV), such as Rous sarcoma virus (RSV) or B77, have yielded large amounts of these viruses. Purified virions were prepared in most cases by simple centrifugation steps and lysed with nonionic
Human immunodeficiency virus type-2 (HIV-2)
HIV-2 was first isolated from West African AIDS patients in 1986 (Clavel et al., 1986) and has been confined mainly to this geographical zone ever since. Nevertheless, in most West African countries, HIV-2 infections are increasingly being overtaken by infections with HIV-1. The two viruses infect mainly CD4 T cells and bear considerable homology in both structure and sequence. HIV-2, like HIV-1, is thought to have passed to humans in the past century from simian immunodeficiency virus
Mouse mammary tumor virus (MMTV)
MMTV was the first mammalian retrovirus isolated. It is unique among retroviruses in its ability to propagate in mammary epithelial cells and function as a carcinogenic agent due to the transcriptional regulation by steroid hormones. MMTV is the only infectious retrovirus that has a distinct type B morphology and was isolated as both an endogenous and an exogenous virus. In betaretroviruses, the synthesis of the Gag-Pro-Pol polyprotein precursor involves two translational frameshift events (
Human T cell lymphotropic virus type I (HTLV-I)
HTLV-I is one of the very few retroviruses that are associated with human diseases. This oncogenic retrovirus was associated with adult T-leukemia/lymphoma as well as with other human chronic diseases. Therefore, it is quite surprising that despite the clinical importance of HTLV-I, the research performed on its RT is quite limited. The virion-associated enzyme was reported to have a molecular mass of about 95 kDa (Rho et al., 1981). However, the recombinant expression of HTLV-I RT was
Spumaretroviruses
Spumaretroviruses (often called foamy viruses) represent a unique group of retroviruses with few properties distinct from all other retroviruses, collectively called orthoretroviruses. In all orthoretroviruses, the pol gene products, which contain RT, are synthesized as Gag-Pol polyprotein precursors, which are cleaved later on to functional enzymes during viral budding or release. In contrast, the Pol protein of spumaretroviruses is translated directly from a spliced messenger RNA and lacks
Acknowledgements
We thank Orna Avidan and Dr. Iris Oz-Gleenberg from our laboratory for the critical reading of this manuscript.
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2017, Virus ResearchCitation Excerpt :Although the proteolytic events leading to the formation of p66/p51 in vivo have not been demonstrated, p66 homodimers can be converted to p66/p51 in vitro by the action of the viral PR. Similar heterodimeric compositions have been described for RTs of HIV-2 (p68/p55), simian immunodeficiency virus (SIV) (p66/p51), FIV (p67/p54) and bovine immunodeficiency virus (BIV) (p64/p51) (Hizi and Herschhorn, 2008). Biochemical studies have shown that HIV-1 RT undergoes a complex maturation process that includes three basic steps: (i) domain rearrangements; (ii) dimerization; and (iii) subunit-selective RNase H proteolysis (for a recent review, see London, 2016).
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A. Hizi is an incumbent of The Gregorio and Dora Shapira Chair for the Research of Malignancies at Tel-Aviv University.