%0 Journal Article
%T Retroviral Env Glycoprotein Trafficking and Incorporation into Virions
%A Tsutomu Murakami
%J Molecular Biology International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/682850
%X Together with the Gag protein, the Env glycoprotein is a major retroviral structural protein and is essential for forming infectious virus particles. Env is synthesized, processed, and transported to certain microdomains at the plasma membrane and takes advantage of the same host machinery for its trafficking as that used by cellular glycoproteins. Incorporation of Env into progeny virions is probably mediated by the interaction between Env and Gag, in some cases with the additional involvement of certain host factors. Although several general models have been proposed to explain the incorporation of retroviral Env glycoproteins into virions, the actual mechanism for this process is still unclear, partly because structural data on the Env protein cytoplasmic tail is lacking. This paper presents the current understanding of the synthesis, trafficking, and virion incorporation of retroviral Env proteins. 1. Introduction All replication-competent retroviruses encode genes for three major proteins: Gag, Pol, and Env. Complex retroviruses, such as human immunodeficiency virus type 1 (HIV-1), encode additional regulatory and accessory proteins required for efficient replication in host cell or the infected host organism. Gag, an essential retroviral protein, is necessary and sufficient for the assembly, budding, and release of virus-like particles (VLPs) in all types of retroviruses except the spumaviruses. Gag is synthesized on cytosolic ribosomes and is assembled as a polyprotein precursor. During and/or shortly after budding and release, the polyprotein is cleaved into several domains by the viral protease (Figure 1) as reviewed in [1¨C3]. The major domains of the precursor Gag are the matrix (MA), capsid (CA), and nucleocapsid (NC). The primary role of the N-terminal MA domain is targeting of the Gag precursor protein to the site of assembly, typically the plasma membrane (PM). In general, electrostatic interactions between basic amino acid residues in MA and the acidic inner leaflet of the PM are important for Gag-membrane targeting [4, 5]. In the case of HIV-1, the N-terminal myristate group and a cluster of basic residues in the MA domain of the HIV-1 Gag that interacts with phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) together target the Gag precursor Pr55Gag to the PM [6, 7]. Although the Gag-membrane targeting of both murine leukemia virus (MLV) and Mason-Pfizer monkey virus (MPMV) is also affected by PI(4,5)P2 modulation [8, 9], it has been reported that the membrane targeting of Rous sarcoma virus (RSV) and human T-lymphotropic virus type 1
%U http://www.hindawi.com/journals/mbi/2012/682850/