Differential Incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and Major Histocompatibility Complex Class I and II Molecules into Human Immunodeficiency Virus Type 1 Virions and Microvesicles: Implications for Viral Pathogenesis and Immune Regulation

Esser, Mark T.; Graham, David R.; Coren, Lori V.; Trubey, Charles M.; Bess, Julian W.; Arthur, Larry O.; Ott, David E.; Lifson, Jeffrey D.

doi:10.1128/jvi.75.13.6173-6182.2001

Cited by 151 publications

(161 citation statements)

References 46 publications

Supporting

Mentioning

153

Contrasting

Order By: Relevance

“…[26][27][28][29] We investigated whether this property could be exploited so that molecules incorporated into the retroviral envelope could be used to redirect binding and transduction of viruses to target cells specifically expressing the appropriate receptor ( Figure 1). To this end we constructed an ecotropic retroviral producer cell line expressing the membrane-bound form of human stem cell factor (mbSCF).…”

Section: Resultsmentioning

confidence: 99%

Targeted retroviral transduction of c-kit+ hematopoietic cells using novel ligand display technology

Chandrashekran

Gordon

Casimir

2004

Blood

View full text Add to dashboard Cite

Gene therapy for a wide variety of disorders would be greatly enhanced by the development of vectors that could be targeted for gene delivery to specific populations of cells. We describe here high-efficiency targeted transduction based on a novel targeting strategy that exploits the ability of retroviruses to incorporate host cell proteins into the surface of the viral particle as they bud through the plasma membrane. Ecotropic retroviral particles produced in cells engineered to express the membrane-bound form of stem cell factor ( IntroductionThe development of retroviral vectors that are targeted to transduce only specific cell types has been the goal of many investigators working in the field of gene therapy. [1][2][3][4][5] The availability of such vectors would revolutionize the field, opening up new avenues for gene therapy in acquired and inherited disorders by enabling in vivo delivery of therapeutic molecules to specific populations of target cells. Novel approaches to drug delivery and for use in vaccines also become possible through display of molecules on the retroviral surface. Over a period of around a decade, however, this goal has proven highly elusive. Virtually all attempts to target specific cell types have logically focused on modification of the retroviral envelope protein, as this complex glycoprotein is established to determine viral host range and facilitate virus entry though membrane fusion. 2,4,5 These modifications can be the simple substitution of the envelope protein for one from another retrovirus or other enveloped virus, such as vesicular stomatitis virus (VSV) 6 , a process referred to as pseudotyping. 2 More recently, attempts have been made to deliberately engineer envelope proteins to redirect their binding to new cell surface molecules. 4 This has involved making N-terminal extensions, insertions, or replacements to regions of the envelope protein. Commonly used modifications have been incorporation of growth factor-binding regions [7][8][9][10][11][12] or the addition of single-chain antibodies. [13][14][15][16][17] While many of these modifications have successfully redirected viral binding, this has invariably been achieved at the expense of infectivity to the extent that targeted binding actually inhibited viral entry. This property has actually been used to advantage in an approach referred to as "inverse targeting." 10,18 A number of reports, however, have indicated that low levels of targeted transduction may be achievable by coexpression of an ecotropic envelope in conjunction with the modified envelope protein. 7,9,16,19 To circumvent the problems associated with envelope modification, we have developed an alternative strategy, exploiting the natural budding mechanism of the virus to insert new binding ligands into the viral surface. We describe here successful and efficient specific targeting of transduction to human cells expressing stem cell factor (SCF) receptor (c-kit) by ecotropic retroviruses bearing surface stem cell factor. Materials and methods Cytokine...

show abstract

Section: Resultsmentioning

confidence: 99%

Targeted retroviral transduction of c-kit+ hematopoietic cells using novel ligand display technology

Chandrashekran

Gordon

Casimir

2004

Blood

View full text Add to dashboard Cite

show abstract

“…At the same time, upregulation of MHC-II may also enhance infectivity mediated by high density of MHC-II on macrophages and increased number of virions in a dynamic immunoregulatory response [72]. HIV-1 infection has also been found to upregulate MHC-II expression in T and B cell lines, macrophages and peripheral blood mononuclear cells (PBMC) without significantly altering CD80/86 expression [42]. Moreover, increased expression of both MHC-I and II antigens has been observed in Maedi-visna virus (MVV) infected pulmonary alveolar macrophages, whereas sheep choroid plexus cells only demonstrated the upregulation of MHC-I [99].…”

Section: Altered Mhc Response During Viral Infectionmentioning

confidence: 99%

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

et al. 2013

View full text Add to dashboard Cite

The mammalian host immune system has wide array of defence mechanisms against viral infections. Depending on host immunity and the extent of viral persistence, either the host immune cells might clear/restrict the viral load and disease progression or the virus might evade host immunity by down regulating host immune effector response(s). Viral antigen processing and presentation in the host cells through major histocompatibility complex (MHC) elicit subsequent anti-viral effector T cell response(s). However, modulation of such response(s) might generate one of the important viral immune evasion strategies. Viral peptides are mostly generated by proteolytic cleavage in the cytosol of the infected host cells. CD8 ? T lymphocytes play critical role in the detection of viral infection by recognizing these peptides displayed at the plasma membrane by MHC-I molecules. The present review summarises the current knowledge on the regulation of mammalian host innate and adaptive immune components, which are operative in defence mechanisms against viral infections and the variety of strategies that viruses have evolved to escape host cell immunity. The understanding of viral immune evasion strategies is important for designing anti-viral immunotherapies.

show abstract

“…Magnetic beads were pelleted with a magnetic plate (Dynal Biotech), and 125 l of the cleared supernatants was loaded on an ELISA plate for p24 measurement, as mentioned above. Because CD45 has been shown to be excluded from HIV-1 (40,41), magnetic beads coated with an isotype-matched Ab specific for human CD45RO (clone UCHL-1) were used as negative controls.…”

Section: Virus Capture Assaymentioning

confidence: 99%

HIV Type 1 Can Act as an APC upon Acquisition from the Host Cell of Peptide-Loaded HLA-DR and CD86 Molecules

Roy

Martin

Giguère

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

It is well documented that a wide range of host-derived cell surface constituents is inserted within HIV type 1 (HIV-1) and located on the exterior of the virion. Although no virus-associated protein of host origin has been shown to be absolutely required for virus replication, studies have revealed that many of these proteins are functional and can affect several steps of the virus life cycle. In this study, we found that HIV-1 acquires peptide-loaded class II MHC (MHC-II) and the costimulatory CD86 molecules from the host cell. Moreover, we present evidence that virions bearing such peptide-loaded MHC-II and CD86 proteins can lead to activation of the transcription factors NF-κB and NF-AT in an Ag-specific human T cell line. A linear correlation was found between activation of NF-κB and the amount of peptide-loaded MHC-II molecules inserted within HIV-1. Finally, transcription of unintegrated and integrated HIV-1 DNA was promoted upon exposure of peptide-specific human T cells to viruses bearing both peptide-loaded MHC-II and CD86 proteins. These data suggest that HIV-1 can operate as an APC depending on the nature of virus-anchored host cell membrane components. It can be proposed that HIV-1 can manipulate one of its primary targets through the process of incorporation of host-derived proteins.

show abstract

Differential Incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and Major Histocompatibility Complex Class I and II Molecules into Human Immunodeficiency Virus Type 1 Virions and Microvesicles: Implications for Viral Pathogenesis and Immune Regulation

Abstract: Human immunodeficiency virus (HIV) infection results in a functional impairment of CD4

Cited by 151 publications

References 46 publications

Targeted retroviral transduction of c-kit+ hematopoietic cells using novel ligand display technology

Targeted retroviral transduction of c-kit+ hematopoietic cells using novel ligand display technology

Immune Regulation and Evasion of Mammalian Host Cell Immunity During Viral Infection

HIV Type 1 Can Act as an APC upon Acquisition from the Host Cell of Peptide-Loaded HLA-DR and CD86 Molecules

Contact Info

Product

Resources

About