The Pseudotypic Paradox

Závada, Jan

doi:10.1099/0022-1317-63-1-15

Cited by 111 publications

(54 citation statements)

References 25 publications

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“…It has long been known that enveloped viruses can incorporate or exclude host cell membrane proteins during the budding process (48), raising the important question of the functional significance of assembly of a host membrane protein in a virion envelope. We have shown that the integral transmembrane protein CD46 and the GPI-linked protein CD55 are both abundantly incorporated into VSV and MuV particles.…”

Section: Discussionmentioning

confidence: 99%

Virion-Associated Complement Regulator CD55 Is More Potent than CD46 in Mediating Resistance of Mumps Virus and Vesicular Stomatitis Virus to Neutralization

Johnson

Lyles

Alexander-Miller

et al. 2012

J Virol

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Enveloped viruses can incorporate host cell membrane proteins during the budding process. Here we demonstrate that mumps virus (MuV) and vesicular stomatitis virus (VSV) assemble to include CD46 and CD55, two host cell regulators which inhibit propagation of complement pathways through distinct mechanisms. Using viruses which incorporated CD46 alone, CD55 alone, or both CD46 and CD55, we have tested the relative contribution of these regulators in resistance to complement-mediated neutralization. Virion-associated CD46 and CD55 were biologically active, with VSV showing higher levels of activity of both cofactors, which promoted factor I-mediated cleavage of C3b into iC3b as well as decay-accelerating factor (DAF) activity against the C3 convertase, than MuV. Time courses of in vitro neutralization with normal human serum (NHS) showed that both regulators could delay neutralization, but viruses containing CD46 alone were neutralized faster and more completely than viruses containing CD55 alone. A dominant inhibitory role for CD55 was most evident for VSV, where virus containing CD55 alone was not substantially different in neutralization kinetics from virus harboring both regulators. Electron microscopy showed that VSV neutralization proceeded through virion aggregation followed by lysis, with virion-associated CD55 providing a delay in both aggregation and lysis more substantial than that conferred by CD46. Our results demonstrate the functional significance of incorporation of host cell factors during virion envelope assembly. They also define pathways of virus complement-mediated neutralization and suggest the design of more effective viral vectors.

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Section: Discussionmentioning

confidence: 99%

Virion-Associated Complement Regulator CD55 Is More Potent than CD46 in Mediating Resistance of Mumps Virus and Vesicular Stomatitis Virus to Neutralization

Johnson

Lyles

Alexander-Miller

et al. 2012

J Virol

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“…One mechanism for expanding the cellular tropism of enveloped viruses is through the formation of phenotypically mixed particles or pseudotypes, a process that commonly occurs during viral assembly in cells infected with two or more viruses [Zavada, 1982]. Human immunodeficiency virus type 1 (HIV-1) has long been known to form pseudotypes by the incorporation of heterologous GPs through phenotypic mixing, allowing an extension of the host range of such virions beyond cells that express the CD4 receptor and an appropriate coreceptor.…”

Section: Expanding the Tropism Of Lentiviruses Through Pseudotypingmentioning

confidence: 99%

Altering the Tropism of Lentiviral Vectors through Pseudotyping

Cronin

Zhang²,

Reiser³

2005

CGT

469

338

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The host range of retroviral vectors including lentiviral vectors can be expanded or altered by a process known as pseudotyping. Pseudotyped lentiviral vectors consist of vector particles bearing glycoproteins (GPs) derived from other enveloped viruses. Such particles possess the tropism of the virus from which the GP was derived. For example, to exploit the natural neural tropism of rabies virus, vectors designed to target the central nervous system have been pseudotyped using rabies virusderived GPs. Among the first and still most widely used GPs for pseudotyping lentiviral vectors is the vesicular stomatitis virus GP (VSV-G), due to the very broad tropism and stability of the resulting pseudotypes. Pseudotypes involving VSV-G have become effectively the standard for evaluating the efficiency of other pseudotypes. This review samples a few of the more prominent examples from the ever-expanding list of published lentiviral pseudotypes, noting comparisons made with pseudotypes involving VSV-G in terms of titer, viral particle stability, toxicity, and host-cell specificity. Particular attention is paid to publications of successfully targeting a specific organ or cell types.

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“…Although the mechanism by which HIV-1 acquires HLA class II DR is not known, one possibility is that it is merely incorporated by its proximity to the budding virion. However, many host proteins appear to be excluded from enveloped viruses in general (38). Interestingly, only HLA class II DR is appreciably incorporated into virions, even when the other isotypes of HLA class II (DP and DQ) are present on the surface of cells (2,8,14,34).…”

mentioning

confidence: 99%

Efficient Incorporation of HLA Class II onto Human Immunodeficiency Virus Type 1 Requires Envelope Glycoprotein Packaging

Poon

Coren

Ott

2000

J Virol

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HLA class II DR is one of the most abundant cell surface proteins incorporated onto human immunodeficiency virus type 1 (HIV-1) during budding. The mechanism for HLA class II protein incorporation is not known and may involve a viral protein. To determine whether Env affects HLA class II protein incorporation, HIV-1 virions, either with or without Env on their surface, were produced from HLA class II-expressing cells and analyzed by whole-virus immunoprecipitation with antisera against HLA class II proteins. HLA class II proteins were detected on virions only when wild-type Env was incorporated, while similar experiments showed that HLA class I proteins were incorporated independent of Env packaging. Therefore, the packaging of HIV-1 Env protein is required for the efficient incorporation of HLA class II but not class I proteins into the virion. Analysis of two Env mutants revealed that the presence of a 43-amino-acid sequence between amino acids 708 and 750 in the gp41 TM cytoplasmic tail was required for efficient incorporation of HLA class II proteins. These data show that HIV-1 actively incorporates HLA class II proteins in a process that, either directly or indirectly, requires Env.Human immunodeficiency virus type 1 (HIV-1) acquires surface glycoproteins, including Env, by budding through the plasma membrane (reviewed in reference 35). Env is a complex made up of the surface glycoprotein gp120 SU noncovalently bound to the gp41 TM transmembrane (TM) protein. This complex binds to CD4 and various coreceptors and allows for viral entry by mediating virus-cell membrane fusion (reviewed in reference 19). Unlike type C retroviral TM proteins, gp41TM has a relatively long cytoplasmic C terminus (tail) that has been shown to induce cytopathic effects and affect the packaging of Env into the virion (9,12,21,36,37).In addition to Env, many different cellular proteins have been detected on the surface of HIV-1 (reviewed in reference 24). Human leukocyte antigen (HLA) class II DR is the most commonly detected and the most abundant host protein on HIV-1 propagated in cell culture and on virus isolated from patient plasma (24,33). Based on biochemical analysis, HLA class II DR may be present at approximately 1.5 to 2 times the level of gp120 SU on the surface of HIV-1 produced from the H9 human T-cell line (2). Although the mechanism by which HIV-1 acquires HLA class II DR is not known, one possibility is that it is merely incorporated by its proximity to the budding virion. However, many host proteins appear to be excluded from enveloped viruses in general (38). Interestingly, only HLA class II DR is appreciably incorporated into virions, even when the other isotypes of HLA class II (DP and DQ) are present on the surface of cells (2,8,14,34). While these results imply that HLA class II DR is specifically incorporated into the virion, this possibility has not been demonstrated. Expression of Env and HLA class II protein incorporation.One possible mechanism for HLA class II protein incorporation is that the packaging of...

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The Pseudotypic Paradox

Cited by 111 publications

References 25 publications

Virion-Associated Complement Regulator CD55 Is More Potent than CD46 in Mediating Resistance of Mumps Virus and Vesicular Stomatitis Virus to Neutralization

Virion-Associated Complement Regulator CD55 Is More Potent than CD46 in Mediating Resistance of Mumps Virus and Vesicular Stomatitis Virus to Neutralization

Altering the Tropism of Lentiviral Vectors through Pseudotyping

Efficient Incorporation of HLA Class II onto Human Immunodeficiency Virus Type 1 Requires Envelope Glycoprotein Packaging

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