The pH independence of mammalian retrovirus infection

McClure, Myra O.; Sommerfelt, Maja A.; Marsh, Mark; Weiss, Robin A.

doi:10.1099/0022-1317-71-4-767

Cited by 199 publications

(248 citation statements)

References 51 publications

(58 reference statements)

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“…One clue may come from the fact that, unlike many other onco-retroviruses, ecotropic virus entry has been shown in some circumstances to be pH dependent, indicating that rather than interaction at the plasma membrane, an endosomal entry route is possible. 39 Late endosomes have a low internal pH, which could be instrumental in triggering the conformational changes required for fusion.…”

Section: Discussionmentioning

confidence: 99%

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

Chandrashekran

Gordon

Casimir

2004

Blood

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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...

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Section: Discussionmentioning

confidence: 99%

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

Chandrashekran

Gordon

Casimir

2004

Blood

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“…Virions pseudotyped with envelope proteins, such as VSV-G, which require endosomal uptake, could bypass a block which targets Nef-and gPr80-defective virions that fuse directly at the cell membrane (28,29). Interestingly, the entry of MLV-E has been described to occur via endocytic vesicles in a cell-type dependent manner (52,53), a property which might explain the target cell-dependent variability of the gPr80 activity observed on MLV-E and the lack of Nef requirement for HIV-1(MLV-E) infecting HT1080 cells. (ii) The requirement for gPr80 or Nef is similarly determined by the producer cell type (Fig.…”

Section: Discussionmentioning

confidence: 99%

MLV glycosylated-Gag is an infectivity factor that rescues Nef-deficient HIV-1

Pizzato

2010

Proc. Natl. Acad. Sci. U.S.A.

102

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Optimal infectivity of HIV-1 virions requires synthesis of the HIV-1 regulatory protein Nef in some producer cells but not others. A survey of 18 lymphoid cell lines found that Nef was dispensable in three, each of which harbored gammaretroviruses. Nef-dependent cell lines were rendered Nef-independent by a cell-free supernatant from the independent lines or by transfection of cloned murine leukemia virus (MLV). Analysis of MLV deletion mutations identified glycosylated gag (glycogag) as the factor that rescues Nef-defective HIV-1 virions. Glycogag was also demonstrated to be required for the infectivity of MLV virions produced in lymphoid cells. Direct comparison of Nef and glycogag revealed identical dependence for activity on Env-pseudotype and producer cell type. The two proteins colocalize within cells, and both increase the yield of viral cDNA in target cells. The functional similarity of Nef and glycogag is a compelling example of convergent evolution in which two structurally unrelated proteins provide a function necessary for virion infectivity in lymphoid cells.

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“…In support of this, enveloped viruses (HSV-1, MLV, and VSV-G HIV-1) were able to infect GFP-VCA-positive cells as efficient as GFP-positive cells ( Figures 1E and 2B). In particular, when HSV-1 and ampho MLV enter cells, like HIV-1, the membrane fusion takes place at the cell surface (Fuller and Spear, 1987;McClure et al, 1990;Wittels and Spear, 1991;Nussbaum et al, 1993). These data indicated that the virus-cell membrane fusion was not inhibited by GFP-VCA.…”

Section: The Efficiency Of the Membrane Fusion Is Not Negatively Affementioning

confidence: 99%

Inhibiting the Arp2/3 Complex Limits Infection of Both Intracellular Mature Vaccinia Virus and Primate Lentiviruses

Komano

Miyauchi

Matsuda

et al. 2004

MBoC

100

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Characterizing cellular factors involved in the life cycle of human immunodeficiency virus type 1 (HIV-1) is an initial step toward controlling replication of HIV-1. Actin polymerization mediated by the Arp2/3 complex has been found to play a critical role in some pathogens' intracellular motility. We have asked whether this complex also contributes to the viral life cycles including that of HIV-1. We have used both the acidic domains from actin-related protein (Arp) 2/3 complex-binding proteins such as the Wiscott-Aldrich syndrome protein (N-WASP) or cortactin, and siRNA directing toward Arp2 to inhibit viral infection. HIV-1, simian immunodeficiency virus (SIV), and intracellular mature vaccinia virus (IMV) were sensitive to inhibition of the Arp2/3 complex, whereas MLV, HSV-1, and adenovirus were not. Interestingly, pseudotyping HIV-1 with vesicular stomatitis virus G protein (VSV-G) overcame this inhibition. Constitutive inhibition of the Arp2/3 complex in the T-cell line H9 also blocked replication of HIV-1. These data suggested the existence of an Arp2/3 complex-dependent event during the early phase of the life cycles of both primate lentiviruses and IMV. Inhibiting the HIV-1's ability to activate Arp2/3 complex could be a potential chemotherapeutic intervention for acquired immunodeficiency syndrome (AIDS)

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The pH independence of mammalian retrovirus infection

Cited by 199 publications

References 51 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

MLV glycosylated-Gag is an infectivity factor that rescues Nef-deficient HIV-1

Inhibiting the Arp2/3 Complex Limits Infection of Both Intracellular Mature Vaccinia Virus and Primate Lentiviruses

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