Efficient Infection Mediated by Viral Receptors Incorporated into Retroviral Particles

Abstract

Many host cell surface proteins, including viral receptors, are incorporated into enveloped viruses. To address the functional significance of these host proteins, murine leukemia viruses containing the cellular receptors for Rous sarcoma virus (Tva) or ecotropic murine leukemia virus (MCAT-1) were produced. These receptor-pseudotyped viruses efficiently infect cells expressing the cognate viral envelope glycoproteins, with titers of up to 105 infectious units per milliliter for the Tva pseudotypes. Receptor and viral glycoprotein specificity and functional requirements are maintained, suggesting that receptor pseudotype infection recapitulates events of normal viral entry. The ability of the Tva and MCAT-1 pseudotypes to infect cells efficiently suggests that, in contrast to human immunodeficiency virus type 1 entry, neither of these retroviral receptors requires a coreceptor for membrane fusion. In addition, the ability of receptor pseudotypes to target infected cells suggests that they may be useful therapeutic reagents for directing infection of viral vectors. Receptor-pseudotyped viruses may be useful for identifying new viral receptors or for defining functional requirements of known receptors. Moreover, this work suggests that the production of receptor pseudotypes in vivo could provide a mechanism for expanded viral tropism with potential effects on the pathogenesis and evolution of the virus.

Production and Characterization of a Soluble, Active Form of Tva, the Subgroup A Avian Sarcoma and Leukosis Virus Receptor

“…The mechanism of sTva inhibition of ASLV(A) infection appears to be by irreversible inactivation of the ASLV virion. In sharp contrast to CD4, which requires a coreceptor for HIV-1 infectivity, Tva appears to be necessary and sufficient to mediate ASLV(A) entry (3,7,72). Binding of sTva to EnvA induces a conformational change in the SU subunit, exposing previously inaccessible protease sites (28), and leads to the formation of stable, higher-order oligomers of the TM subunit (3a) reminiscent of structures for the putative fusogenic forms of influenza HA2 (11,13), Ebola virus GP2 subunits (67), and the murine leukemia virus (MLV) (26) and HIV-1 TM subunits (12,60,68).…”

Soluble Forms of the Subgroup A Avian Leukosis Virus [ALV(A)] Receptor Tva Significantly Inhibit ALV(A) Infection In Vitro and In Vivo

“…Cells expressing the sTva proteins showed significant resistance to ALV(A) infection, presumably due to the secreted receptor proteins binding the glycoproteins of the invading virion, thus blocking the interactions of the virus and the mem- brane-bound Tva, a form of receptor interference. Tva has been hypothesized to be necessary and sufficient to mediate ALV(A) entry (3,6,50). Several possible mechanisms could account for the sTva inhibition of ALV(A) entry.…”

Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles

“…Retaining the native structure of multispanning membrane proteins during immunization (and later phage-panning steps) is vital for eliciting functionally relevant mAbs, which usually recognize conformational structures on the extracellular membrane protein face. VLPs are noninfectious lipid-enveloped retroviral particles that can present intact multispanning membrane proteins on their surface with native topology and conformation (19)(20)(21). VLPs can capture high levels of structurally intact GPCRs, ion channels, and transporters when the viral particles bud from the plasma membrane and are potent immunogens due to their particulate structure and multivalent epitope organization (22,23).…”