Receptors and entry cofactors for retroviruses include single and multiple transmembrane-spanning proteins as well as newly described glycophosphatidylinositol-anchored and secreted proteins

Abstract

In the past few years, many retrovirus receptors, coreceptors, and cofactors have been identified. These molecules are important for some aspects of viral entry, although in some cases it remains to be determined whether they are required for binding or postbinding stages in entry, such as fusion. There are certain common features to the molecules that many retroviruses use to gain entry into the cell. For example, the receptors for most mammalian oncoretroviruses are multiple membrane-spanning transport proteins. However, avian retroviruses use single-pass membrane proteins, and a sheep retrovirus uses a glycosylphosphatidylinositol-anchored molecule as its receptor. For some retroviruses, particularly the lentiviruses, two cell surface molecules are required for efficient entry. More recently, a soluble protein that is required for viral entry has been identified for a feline oncoretrovirus. In this review, we will focus on the various strategies used by mammalian retroviruses to gain entry into the cell. The choice of receptors will also be discussed in light of pressures that drive viral evolution and persistence.

FIG. 1

Schematic depiction of the different classes of retroviral receptors. The general class of receptor is described above the cartoon, which depicts the predicted topology of a specific receptor of that class, as indicated below the cartoon. For the indicated receptor, its commonly assumed role in binding and/or fusion is indicated. A question mark indicates that there are no published data on whether the molecule is a binding or fusion receptor. At the bottom of the figure, other members of the general receptor class are shown, using colors to refer to the specific molecule in the cartoon above. These receptors are assigned to a specific class on the basis of whether they are single- or multiple-membrane proteins, not because they have an identical structure as the receptor shown. For example, the members of the multiple TM class may vary in the predicted number of TM domains. Only two coreceptors for lentiviruses are mentioned, and the reader is referred to references and for a more complete list. Also, as discussed in the text, there are some cases where lentiviruses use only the coreceptor and not CD4 to infect cells. This is not specifically indicated, although such cases would be best described as falling in the class of multiple TM receptors.

FIG. 2

Amino acid sequence similarity among retrovirus envelope proteins. Envelope proteins, including the endoplasmic reticulum signal sequences, were compared using CLUSTAL W. The scale bar indicates 10% sequence difference. Viruses that are shown in the same color use a similar receptor. The receptors for viruses shown in black remain to be identified. Abbreviations: MoMLV, Moloney MLV; AKV, AKR MLV; MCF, mink cell focus-forming virus; NZB, New Zealand black mouse MLV; AM-MLV, amphotropic MLV; 10A1, 10A1 MLV; MDEV, M. dunni endogenous virus; ENTV, enzootic nasal tumor virus; MMTV, mouse mammary tumor virus; RSV-A, RSV-B, and RSV-D, Rous sarcoma virus types A, B, and D; HFV, “human” foamy virus (actually of simian origin); WDSV, walleye dermal sarcoma virus; BLV, bovine leukemia virus; RD114, cat endogenous virus RD-114; MPMV, Mason-Pfizer monkey virus, also called SRV-3; SNV, avian spleen necrosis virus;

FIG. 3

Evolution of FeLV-B, GALV, and MLV. Viruses that use only Pit1 as a receptor are those that developed from recombination between exogenous retroviruses and endogenous retroviral sequences. FeLV-B is a recombinant virus derived from the exchange of genetic material between exogenous FeLV-A and endogenous FeLV-related envelope sequences. 10A1 MLV arose as a consequence of recombination between A-MLV and an endogenous murine retroviral sequence, and GALVs contain envelope sequences derived from a certain Southeast Asian species of feral mice harboring MLV class I endogenous retroviral sequences.