Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Ranaviruses (RV, Iridoviridae) are large double-stranded DNA viruses that infect fish, amphibians and reptiles. For ecological and commercial reasons, considerable attention has been drawn to the increasing prevalence of ranaviral infections of wild populations and in aquacultural settings. Importantly, RVs appear to be capable of crossing species barriers of numerous poikilotherms, suggesting that these pathogens possess a broad host range and potent immune evasion mechanisms. Indeed, while some of the 95-100 predicted ranavirus genes encode putative evasion proteins (e.g., vIFα, vCARD), roughly two-thirds of them do not share significant sequence identity with known viral or eukaryotic genes. Accordingly, the investigation of ranaviral virulence and immune evasion strategies is promising for elucidating potential antiviral targets. In this regard, recombination-based technologies are being employed to knock out gene candidates in the best-characterized RV member, Frog Virus (FV3). Concurrently, by using animal infection models with extensively characterized immune systems, such as the African clawed frog, Xenopus laevis, it is becoming evident that components of innate immunity are at the forefront of virus-host interactions. For example, cells of the macrophage lineage represent important combatants of RV infections while themselves serving as targets for viral infection, maintenance and possibly dissemination. This review focuses on the recent advances in the understanding of the RV immune evasion strategies with emphasis on the roles of the innate immune system in ranaviral infections.
Figure 1. Electron micrographs of peritoneal macrophages from FV3-infected Xenopus laevis adults. Peritoneal leukocytes were collected from frogs 2 days subsequent to infection with 5 × 106 PFU of FV3, processed and visualized under a Hitachi 7650 TEM. (A) Mononucleated macrophage-like cells with an intracellular pool of FV3 virions (arrow, scale bar: 2 μm). (B) A magnified image of the intracellular macrophage pool of FV3 virions (scale bar: 200 nm). (C) A macrophage-like cell shedding viral particles (arrow, scale bar: 2 μm). (D) A magnified image of a virus-shedding macrophage (scale bar: 0.5 μm).
Figure 2. Comparison of Xenopus laevis tadpole and adult peritoneal macrophages. Peritoneal leukocytes were collected from frogs 3 days after elicitation with heat-killed Escherichia coli. Cells were seeded in and allowed to adhere to bottoms of 24 well plates for 3 hours. Non-adherent cells were removed, the adherent cells washed and cultured for further 4 days. Cells were cytospun onto glass slides and Giemsa stained according to standard protocol. Upper panels represent peritoneal macrophages collected from tadpoles and lower panels represent peritoneal macrophages derived from adult frogs.
Figure 3. Comparison of Xenopus laevis tadpole and adult peritoneal macrophages infected by FV3. Peritoneal leukocytes were collected from one adult (A) or from 10 pooled pre-metamorphic tadpoles (B and C) 2 days after FV3 infection by intraperitoneal injection. Cells were fixed, stained with a rabbit anti-53R (green) and DNA dye Hoechst-33258 (blue), then mounted in anti-fade medium and visualized with a Leica DMIRB inverted fluorescence microscope.
Aubertin,
Preparation and properties of an inhibitory extract from frog virus 3 particles.
1973, Pubmed
Aubertin,
Preparation and properties of an inhibitory extract from frog virus 3 particles.
1973,
Pubmed Auffray,
Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior.
2007,
Pubmed Bird,
The first cytokine sequence within cartilaginous fish: IL-1 beta in the small spotted catshark (Scyliorhinus canicula).
2002,
Pubmed Cassatella,
Molecular basis of interferon-gamma and lipopolysaccharide enhancement of phagocyte respiratory burst capability. Studies on the gene expression of several NADPH oxidase components.
1990,
Pubmed Cassatella,
Interferon-gamma activates human neutrophil oxygen metabolism and exocytosis.
1988,
Pubmed Chao,
Histological, ultrastructural, and in situ hybridization study on enlarged cells in grouper Epinephelus hybrids infected by grouper iridovirus in Taiwan (TGIV).
2004,
Pubmed Chen,
Improved knockout methodology reveals that frog virus 3 mutants lacking either the 18K immediate-early gene or the truncated vIF-2alpha gene are defective for replication and growth in vivo.
2011,
Pubmed
,
Xenbase Chinchar,
Family Iridoviridae: poor viral relations no longer.
2009,
Pubmed Chinchar,
Inactivation of frog virus 3 and channel catfish virus by esculentin-2P and ranatuerin-2P, two antimicrobial peptides isolated from frog skin.
2001,
Pubmed Coiras,
Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs.
2009,
Pubmed Collins,
Amphibian decline and extinction: what we know and what we need to learn.
2010,
Pubmed Corradin,
Phagocytosis enhances murine macrophage activation by interferon-gamma and tumor necrosis factor-alpha.
1991,
Pubmed Cuthbertson,
Macrophage products IL-1 alpha, TNF alpha and bFGF may mediate multiple cytopathic effects in the developing eyes of GM-CSF transgenic mice.
1990,
Pubmed Daszak,
Emerging infectious diseases and amphibian population declines.
1999,
Pubmed Elharrar,
[Pathogenesis of the toxic hepatitis of mice provoked by FV 3 (frog virus 3): inhibition of liver macromolecular synthesis (author's transl)].
1973,
Pubmed Essbauer,
Comparison of the eIF-2alpha homologous proteins of seven ranaviruses (Iridoviridae).
2001,
Pubmed Ferreri,
Induction of macrophage TNF alpha, IL-1, IL-6, and PGE2 production by DTH-initiating factors.
1991,
Pubmed Flajnik,
Major histocompatibility complex-encoded class I molecules are absent in immunologically competent Xenopus before metamorphosis.
1986,
Pubmed
,
Xenbase Fremond,
IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection.
2007,
Pubmed Gantress,
Development and characterization of a model system to study amphibian immune responses to iridoviruses.
2003,
Pubmed
,
Xenbase Gendrault,
Penetration and uncoating of frog virus 3 (FV3) in cultured rat Kupffer cells.
1981,
Pubmed George,
Characterization of the heparin-mediated activation of PKR, the interferon-inducible RNA-dependent protein kinase.
1996,
Pubmed Gil,
Induction of apoptosis by double-stranded-RNA-dependent protein kinase (PKR) involves the alpha subunit of eukaryotic translation initiation factor 2 and NF-kappaB.
1999,
Pubmed Gordon,
Alternative activation of macrophages: mechanism and functions.
2010,
Pubmed Gousset,
Real-time visualization of HIV-1 GAG trafficking in infected macrophages.
2008,
Pubmed Gray,
Ecology and pathology of amphibian ranaviruses.
2009,
Pubmed
,
Xenbase Grayfer,
Molecular characterization, expression and functional analysis of goldfish (Carassius aurutus L.) interferon gamma.
2009,
Pubmed Grayfer,
Comparison of macrophage antimicrobial responses induced by type II interferons of the goldfish (Carassius auratus L.).
2010,
Pubmed Grayfer,
Characterization and functional analysis of goldfish (Carassius auratus L.) tumor necrosis factor-alpha.
2008,
Pubmed Green,
Epizootiology of sixty-four amphibian morbidity and mortality events in the USA, 1996-2001.
2002,
Pubmed Groot,
Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses.
2008,
Pubmed Gut,
Frog virus 3 induces a fatal hepatitis in rats.
1981,
Pubmed Hagmann,
Leukotrienes as mediators in frog virus 3-induced hepatitis in rats.
1987,
Pubmed Hirono,
Molecular cloning, characterization, and expression of TNF cDNA and gene from Japanese flounder Paralychthys olivaceus.
2000,
Pubmed Huang,
Roles of stress-activated protein kinases in the replication of Singapore grouper iridovirus and regulation of the inflammatory responses in grouper cells.
2011,
Pubmed Igawa,
An unexpected discovery of two interferon gamma-like genes along with interleukin (IL)-22 and -26 from teleost: IL-22 and -26 genes have been described for the first time outside mammals.
2006,
Pubmed Ishibe,
Comparative analysis of the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) from macrophages exposed to high virulent and low virulent strains of Edwardsiella tarda.
2009,
Pubmed Itoh,
Induction of TNF-like factor by murine macrophage-like cell line J774.1 on treatment with Sarcophaga lectin.
1984,
Pubmed Jancovich,
Innate immune evasion mediated by the Ambystoma tigrinum virus eukaryotic translation initiation factor 2alpha homologue.
2011,
Pubmed Kawai,
Antiviral signaling through pattern recognition receptors.
2007,
Pubmed Kawai,
SnapShot: Pattern-recognition receptors.
2007,
Pubmed Kerr,
Nature of inhibitor of cell-free protein synthesis formed in response to interferon and double-stranded RNA.
1977,
Pubmed Kirn,
[FV3 (Frog Virus 3) toxicity for the mouse].
1972,
Pubmed Kirn,
Endocytic capacities of Kupffer cells isolated from the human adult liver.
1982,
Pubmed Kirn,
Inhibition of erythrophagocytosis by cultured rat Kupffer cells infected with frog virus 3.
1980,
Pubmed Langland,
Inhibition of PKR by RNA and DNA viruses.
2006,
Pubmed Liew,
Tumour necrosis factor (TNF-alpha) in leishmaniasis. II. TNF-alpha-induced macrophage leishmanicidal activity is mediated by nitric oxide from L-arginine.
1990,
Pubmed Majji,
Transcriptome analysis of Frog virus 3, the type species of the genus Ranavirus, family Iridoviridae.
2009,
Pubmed Maniero,
Generation of a long-lasting, protective, and neutralizing antibody response to the ranavirus FV3 by the frog Xenopus.
2006,
Pubmed
,
Xenbase McMasters,
Regulation of macrophage TNF alpha, IL-1 beta, and Ia (I-A alpha) mRNA expression during peritonitis is site dependent.
1993,
Pubmed Meurs,
Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon.
1990,
Pubmed Morales,
Characterization of primary and memory CD8 T-cell responses against ranavirus (FV3) in Xenopus laevis.
2007,
Pubmed
,
Xenbase Morales,
Innate immune responses and permissiveness to ranavirus infection of peritoneal leukocytes in the frog Xenopus laevis.
2010,
Pubmed
,
Xenbase Myers,
Regulation of IL-1 and TNF-alpha expression during the differentiation of bone marrow derived macrophage.
1989,
Pubmed Nahrendorf,
The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions.
2007,
Pubmed Nathan,
Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity.
1983,
Pubmed Nishikawa,
Roles of macrophages in programmed cell death and remodeling of tail and body muscle of Xenopus laevis during metamorphosis.
1998,
Pubmed
,
Xenbase Ordás,
Turbot TNFalpha gene: molecular characterization and biological activity of the recombinant protein.
2007,
Pubmed Purcell,
Quantitative expression profiling of immune response genes in rainbow trout following infectious haematopoietic necrosis virus (IHNV) infection or DNA vaccination.
2004,
Pubmed Purcell,
Comprehensive gene expression profiling following DNA vaccination of rainbow trout against infectious hematopoietic necrosis virus.
2006,
Pubmed Robert,
Xenopus laevis: a possible vector of Ranavirus infection?
2007,
Pubmed
,
Xenbase Robert,
Comparative and developmental study of the immune system in Xenopus.
2009,
Pubmed
,
Xenbase Roberts,
Interferon-mediated protein kinase and low-molecular-weight inhibitor of protein synthesis.
1976,
Pubmed Rothenburg,
Characterization of a ranavirus inhibitor of the antiviral protein kinase PKR.
2011,
Pubmed Ruvolo,
Ceramide regulates protein synthesis by a novel mechanism involving the cellular PKR activator RAX.
2001,
Pubmed Shimoda,
A human macrophage hybridoma producing a cytotoxic factor distinct from TNF, LT, and IL-1.
1988,
Pubmed Siwicki,
Effects of iridovirus-like agent on the cell-mediated immunity in sheatfish (Silurus glanis)--an in vitro study.
1999,
Pubmed Stuart,
Status and trends of amphibian declines and extinctions worldwide.
2004,
Pubmed Thompson,
Toll-like receptors, RIG-I-like RNA helicases and the antiviral innate immune response.
2007,
Pubmed Whitley,
Antisense approaches for elucidating ranavirus gene function in an infected fish cell line.
2011,
Pubmed Xiao,
Tumor necrosis factor-alpha gene from mandarin fish, Siniperca chuatsi: molecular cloning, cytotoxicity analysis and expression profile.
2007,
Pubmed Zhao,
Identification of novel functional differences in monocyte subsets using proteomic and transcriptomic methods.
2009,
Pubmed Ziegler-Heitbrock,
The CD14+ CD16+ blood monocytes: their role in infection and inflammation.
2007,
Pubmed
