10 Endonuclease Activity Associated with Reverse Transcriptase of Avian Sarcoma-Leukosis Viruses

Abstract

The pol genes of retroviruses encode reverse transcriptase (RT) polymerase and ribonuclease H (RNase H) domains, integrase (IN), and sometimes the protease (PR) domain. These pol gene products are translated as part of the large gag-pol-encoded precursor polyprotein processed by PR. However, the proteolytic processing strategies differ among retroviruses. In some cases, incomplete processing occurs, forming RT subunits that contain additional domains or activities. For example, RT of Moloney murine leukemia virus (Mo-MLV) is a monomer of 80 kD, whereas the RTs of avian sarcoma-leukosis virus (ASLV) and human immunodeficiency virus (HIV) are heterodimers (see Fig. 1). With the HIV RT, the larger subunit (p66) contains both the polymerase and RNase H domains; the smaller subunit (p51) has only the polymerase, the RNase H domain having been removed by carboxy-terminal processing. The ASLV RT subunits also differ by a carboxy-terminal processing. However, in this case, both (α of 63 kD, and β of 95 kD) contain polymerase and RNase H domains, and the larger subunit includes sequences encoding IN at its carboxyl terminus. The endonuclease activity associated with IN presumably reflects the enzyme’s ability to make single-stranded breaks (nicks) in both host and viral DNAs during the integration reaction. It is the presence of IN sequences on the β subunit of ASLV RT that accounts for the DNA endonuclease activity of this RT. The functional consequences of these differences in pol precursor processing are unknown. The IN domain could, however, contribute to the function of RT αβ in several ways...