Emergence of vertebrate retroviruses and envelope capture

Abstract

Retroviruses are members of the superfamily of retroelements, mobile genetic elements that transpose via an RNA intermediate. However, retroviruses are distinct from other retroelements in that their "transposition" is not confined to single cells but extends to neighboring cells and organisms. As such, the "transposition" of these elements is defined as infection. It appears that a key step in the conversion of a retrotransposon into a retrovirus is the modular acquisition or capture of an envelope glycoprotein (Env) which facilitates dissemination from its initial host cell. Here we present several examples of retroviruses for which envelope capture has been identified. Indeed, capture may explain the notable conservation of env sequences among otherwise phylogenetically distant retroviruses. In a recent example, sequence homologies reported between the env of the phylogenetically distant murine leukemia viruses (MLV) and human T cell leukemia viruses (HTLV) argue in favor of an env capture by the latter. Env acquisition can provide new adaptive properties to replication-competent viruses in addition to altering their host range. Also, the captured env can alter the spectrum of physiological affects of infection in new host cells and organisms. The elucidation of such envelope exchanges and properties thereof should contribute significantly to the clarification of retroviral phylogeny, insight into retroviral pathogenesis, and to the discovery of new retroviruses.

Env-less endogenous retroviruses are genomic superspreaders

“…ERV lineages do not persist indefinitely in their host but rather cease replicating after a predictable time (28): Proliferation and cross species transmission might be regarded as alternate responses to lineage extinction. Among IAPs, we find no cases of cross-species transmission after loss of env, and, indeed, no cases of env capture by env-less vertebrate ERVs are known (29). However, we cannot preclude the possibility that such capture might occur.…”

HTLV-1 tropism and envelope receptor

“…Notably though, alignment of the HTLV-1 SU with that of the Friend-murine leukemia virus (F-MLV) reveals highly conserved microdomains within the SU and underscores a similar general organization of the SU (Kim et al, 2000(Kim et al, , 2004a (Figure 2). Functional evaluation of different SU domains, as delineated in Figure 2, allowed us to demonstrate that, paradoxically to its 'complex' genetic organization, the HTLV SU has a modular organization that is identical to that of simple retroviruses (Battini et al, 1995), with the RBD residing at the SU amino terminal (Kim et al, 2000(Kim et al, , 2004b.…”

“…Basyuk et al (2003) have previously shown that MLV Env redirects endogenous retroviral RNA-Gag trafficking from intracellular lysosomes to exiting endosomes. Based on these observations and several phylogenetic considerations on the dichotomy between the evolutionary pattern of retroviral env genes and the remainder of the retroviral genome (Malik et al, 2000;Benit et al, 2001;Pearson and Rohrmann, 2002;Kim et al, 2004a), we have postulated that infectious gammaretroviruses emerged upon env gene 'capture' by endogenous retrotransposons (Kim et al, 2004a). Thus, it is possible that upon 'capture' of an env gene, intracellular interactions between Env and its cell receptor foster the routing of the virus out of the cell (Kim et al, 2004a).…”

“…Based on these observations and several phylogenetic considerations on the dichotomy between the evolutionary pattern of retroviral env genes and the remainder of the retroviral genome (Malik et al, 2000;Benit et al, 2001;Pearson and Rohrmann, 2002;Kim et al, 2004a), we have postulated that infectious gammaretroviruses emerged upon env gene 'capture' by endogenous retrotransposons (Kim et al, 2004a). Thus, it is possible that upon 'capture' of an env gene, intracellular interactions between Env and its cell receptor foster the routing of the virus out of the cell (Kim et al, 2004a). Therefore, evaluating the contribution of Env-receptor interactions in viral egress might provide additional clues on the exclusive selection by gammaretroviruses and HTLV of nutrient transporters as Env receptors (Tailor et al, 2003).…”

Antibodies to the Envelope Glycoprotein of Human T Cell Leukemia Virus Type 1 Robustly Activate Cell-Mediated Cytotoxic Responses and Directly Neutralize Viral Infectivity at Multiple Steps of the Entry Process

“…Although the crystal structure for HTLV-1 SU has not yet been determined, rigorous examination suggests that the SU is comprised of two autonomously folding domains separated by a proline-rich linker peptide (31)(32)(33)(34)(35)(36). The N-terminal region, also known as the receptor-binding domain (RBD), is necessary and sufficient for binding to Glut-1 on target T cells (21,33).…”