The ‘supervirus’? Lessons from IL-4-expressing poxviruses

Stanford, Marianne M.; McFadden, Grant

doi:10.1016/j.it.2005.04.001

Cited by 26 publications

(27 citation statements)

References 52 publications

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“…Our bicistronic cassette gives the added advantage of precise identification of cells expressing a gene of interest; GFP localization will thus give the opportunity to study host-virus interactions at the singlecell level in vivo. Such studies may have added significance given the renewed interest in vaccines against small pox (Qutaishat and Olson, 2003;Stanford and McFadden, 2005).…”

Section: Discussionmentioning

confidence: 99%

Generation of Recombinant Vaccinia Viruses via Green Fluorescent Protein Selection

Попов

Mirshahidi

Essono

et al. 2009

DNA and Cell Biology

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We developed a rapid method to generate recombinant vaccinia viruses (rVVs) based upon a bicistronic cassette encoding the gene for green fluorescent protein (GFP) and a foreign gene of interest separated by an internal ribosome entry site (IRES). As proof-of-concept, we inserted a mutant env gene of human immunodeficiency virus (HIV) into the cassette, which was cloned into the vaccinia virus (VV) insertion vector pSC59 under the control of the early-late VV synthetic promoter and flanked by disrupted tk gene sequences. To generate rVVs, 293T cells were inoculated with wild-type (wt) VV, followed by transfection of the modified pSC59 vector containing the bicistronic cassette, which allows expression of GFP and the protein of interest. Next, GFPpositive cells were isolated by flow cytometry or by picking under a fluorescent microscope. Thymidine kinasedeficient (Tk À ) 143B cells were then exposed to lysates of GFP-positive 293T cells and cultured in the presence of bromodeoxyuridine. This selection allows only Tk À rVV to remain viable. We demonstrated the success of this GFP selection strategy by expressing high levels of mutant HIV Env. Our approach shortens the time needed to generate rVVs and represents a practical approach to generate recombinant proteins.

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Section: Discussionmentioning

confidence: 99%

Generation of Recombinant Vaccinia Viruses via Green Fluorescent Protein Selection

Попов

Mirshahidi

Essono

et al. 2009

DNA and Cell Biology

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“…The impaired CTL function in T-bet Ϫ/Ϫ mice could be caused directly by T-bet deficiency or could be a secondary effect due to the inadequate CD4 ϩ Th1 help to VV-specific CTLs in the T-bet deficiency. It has been shown that the insertion of IL-4 into vaccinia virus significantly increases the efficiency of the recombinant virus as a pathogen by directly inhibiting the development of Th1 immunity (27). In mice, the expression of IL-4 from the recombinant virus results in a decrease in CTL levels and a delay in viral clearance (26,27).…”

Section: Discussionmentioning

confidence: 99%

T-bet Is Required for Protection against Vaccinia Virus Infection

Matsui

Moriya

Yoshimoto

et al. 2005

J Virol

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The transcription factor T-bet regulates the differentiation of CD4؉ T-helper type 1 (Th1) cells and represses Th2 lineage commitment. Since Th1 cells are crucial in the defense against pathogens, several studies addressed the role of T-bet in immunity to infection using T-bet knockout (T-bet ؊/؊ ) mice. Nevertheless, it is still unclear whether T-bet is required for defense. Although vaccinia virus (VV) has extensively been used as an expression vector and the smallpox vaccine, there is only limited knowledge about immunity to VV infection. The urgency to understand the immune responses has been increased because of concerns about bioterrorism. Here, we show that T-bet is critical in the defense against VV infection as follows: (i) the survival rate of T-bet ؊/؊ mice was lower than that of control littermates postinfection; (ii) T-bet ؊/؊ mice lost more weight postinfection; and (iii) control mice cleared VV faster than T-bet ؊/؊ mice. As expected, a significant Th2 shift was observed in CD4؉ T cells of T-bet ؊/؊ mice. Furthermore, absence of T-bet impaired VV-specific CD8 ؉ cytotoxic T-lymphocyte (CTL) function, including cytolytic activity, antiviral cytokine production, and proliferation. Cytolytic capacity of natural killer (NK) cells was also diminished in T-bet ؊/؊ mice, whereas anti-VV antibody production was not impaired. These data reveal that the enhanced susceptibility to VV infection in T-bet ؊/؊ mice was at least partially due to the Th2 shift of CD4 ؉ T cells and the diminished function of VV-specific CTLs and NK cells but not due to downregulation of antibody production.

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“…Throughout evolutionary history poxviruses have continuously evolved, consequently developing a variety of sophisticated strategies to ensure successful viral replication within the host [38,69,91]. One particular mechanism conceived by MV to subvert the host immune response is carried out by two related sets of immunomodulatory proteins described as virokines and viroreceptors [74,87].…”

Section: Virokines and Viroreceptorsmentioning

confidence: 99%

“…There are many extensive and excellent reviews on the immunomodulatory proteins of poxviruses [42,50,64,69,74,75,87,91,106]. This review will focus primarily on the interactions of MV and its susceptible host, the European rabbit in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host

2007

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-Myxoma virus (MV) is a poxvirus that evolved inSylvilagus lagomorphs, and is the causative agent of myxomatosis in European rabbits (Oryctolagus cuniculus). This virus is not a natural pathogen of O. cuniculus, yet is able to subvert the host rabbit immune system defenses and cause a highly lethal systemic infection. The interaction of MV proteins and the rabbit immune system has been an ideal model to help elucidate host/poxvirus interactions, and has led to a greater understanding of how other poxvirus pathogens are able to cause disease in their respective hosts. This review will examine how MV causes myxomatosis, by examining a selection of the identified immunomodulatory proteins that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts. myxoma virus / immunomodulation / poxvirus / Oryctolagus cuniculus

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The ‘supervirus’? Lessons from IL-4-expressing poxviruses

Cited by 26 publications

References 52 publications

Generation of Recombinant Vaccinia Viruses via Green Fluorescent Protein Selection

Generation of Recombinant Vaccinia Viruses via Green Fluorescent Protein Selection

T-bet Is Required for Protection against Vaccinia Virus Infection

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host

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