Properties of a baboon lymphotropic herpesvirus related to Epstein‐Barr virus

Falk, Lawrence A.; Deinhardt, Friedrich; Nonoyama, Meihan; Wolfe, Lauren G.; Bergholz, Carolyn M.; Лапин, Б. А.; Yakovleva, L. A.; Agrba, V. Z.; Henle, Gertrude; Henle, Werner

doi:10.1002/ijc.2910180611

Cited by 115 publications

(65 citation statements)

References 21 publications

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“…EF3D-MigW LCLs were generated in parallel with EF3D-Ago2 LCLs as previously described (27) and were infected with EBV B95-8. rLCV-infected rhesus macaque rLCLs (211-98 and 309-98) and baboon S594 LCLs (kind gifts of F. Wang) have been described (30,31). Established LCLs were maintained in log phase in RPMI 1640 supplemented with heat-inactivated 12% fetal bovine serum (FBS) and antibiotics.…”

Section: Methodsmentioning

confidence: 99%

Evolutionary Conservation of Primate Lymphocryptovirus MicroRNA Targets

Skalsky

Kang

Linnstaedt

et al. 2014

J Virol

108

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Section: Methodsmentioning

confidence: 99%

Evolutionary Conservation of Primate Lymphocryptovirus MicroRNA Targets

Skalsky

Kang

Linnstaedt

et al. 2014

J Virol

108

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“…Human recombinant IL-2 (20 IU/ml; Proleukin; Chiron) was added on days 1, 3, and 6. For the derivation of stable rhesus B-lymphoblastoid cell lines (B-LCL), PBMC were exposed to herpesvirus papio-containing culture supernatant from the S594 cell line (13,27) in the presence of 1 g of cyclosporine (Sigma)/ml.…”

Section: Methodsmentioning

confidence: 99%

Increased Expression and Immunogenicity of Sequence-Modified Human Immunodeficiency Virus Type 1 gag Gene

Megede¹,

Chen²,

Doe³

et al. 2000

J Virol

173

122

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A major challenge for the next generation of human immunodeficiency virus (HIV) vaccines is the induction of potent, broad, and durable cellular immune responses. The structural protein Gag is highly conserved among the HIV type 1 (HIV-1) gene products and is believed to be an important target for the host cellmediated immune control of the virus during natural infection. Expression of Gag proteins for vaccines has been hampered by the fact that its expression is dependent on the HIV Rev protein and the Rev-responsive element, the latter located on the env transcript. Moreover, the HIV genome employs suboptimal codon usage, which further contributes to the low expression efficiency of viral proteins. In order to achieve high-level Rev-independent expression of the Gag protein, the sequences encoding HIV-1 SF2 p55Gag were modified extensively. First, the viral codons were changed to conform to the codon usage of highly expressed human genes, and second, the residual inhibitory sequences were removed. The resulting modified gag gene showed increases in p55Gag protein expression to levels that ranged from 322-to 966-fold greater than that for the native gene after transient expression of 293 cells. Additional constructs that contained the modified gag in combination with modified protease coding sequences were made, and these showed high-level Rev-independent expression of p55Gag and its cleavage products. Density gradient analysis and electron microscopy further demonstrated that the modified gag and gagprotease genes efficiently expressed particles with the density and morphology expected for HIV virus-like particles. Mice immunized with DNA plasmids containing the modified gag showed Gag-specific antibody and CD8 ؉ cytotoxic T-lymphocyte (CTL) responses that were inducible at doses of input DNA 100-fold lower than those associated with plasmids containing the native gag gene. Most importantly, four of four rhesus monkeys that received two or three immunizations with modified gag plasmid DNA demonstrated substantial Gag-specific CTL responses. These results highlight the useful application of modified gag expression cassettes for increasing the potency of DNA and other gene delivery vaccine approaches against HIV.

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“…Stable rhesus B-lymphoblastoid cell lines (B-LCL) were derived by exposing PBMC to herpesvirus papio-containing culture supernatant from the S594 cell line (13,23) in the presence of 0.5-g/ml cyclosporin A (Sigma, St. Louis, Mo. ).…”

Section: Measurement Of T-cell Responses In Macaquesmentioning

confidence: 99%

Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines

O’Hagan¹,

Singh²,

Ugozzoli³

et al. 2001

J Virol

172

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The effectiveness of cationic microparticles with adsorbed DNA at inducing immune responses was investigated in mice, guinea pigs, and rhesus macaques. Plasmid DNA vaccines encoding human immunodeficiency virus (HIV) Gag and Env adsorbed onto the surface of cationic poly(lactide-coglycolide) (PLG) microparticles were shown to be substantially more potent than corresponding naked DNA vaccines. In mice immunized with HIV gag DNA, adsorption onto PLG increased CD8 ؉ T-cell and antibody responses by ϳ100-and ϳ1,000-fold, respectively. In guinea pigs immunized with HIV env DNA adsorbed onto PLG, antibody responses showed a more rapid onset and achieved markedly higher enzyme-linked immunosorbent assay and neutralizing titers than in animals immunized with naked DNA. DNA vaccines have been shown to induce immune responses and protective immunity in many animal models of infectious disease (for a review, see reference 11). In mice, such responses can often be achieved with low doses (Ͻ1 g) of naked DNA. However, the immunogenicity of DNA vaccines in larger animals (e.g., guinea pigs, rabbits, and nonhuman primates) has been much lower than that observed in mice, even at higher doses of DNA. In human clinical trials, certain DNA vaccines have been shown to induce immune responses (5,19,30), but multiple immunizations of high doses of DNA were required. Therefore, in order to provide protective efficacy in humans, the potency of DNA vaccines needs to be increased. So far, it appears that DNA vaccines are more effective at priming T-cell responses than antibodies, as exemplified by induction of cytotoxic T lymphocytes (CTL) but no antibodies against malaria circumsporozoite protein in humans (30). Similarly, we show here that in mice, human immunodeficiency virus (HIV) gag DNA primed CD8 ϩ T-cell responses at doses of DNA 10-to 100-fold lower than that required for priming of antibody responses. Therefore, technologies aimed at increasing the potency of DNA vaccines need to be especially effective at boosting humoral responses.The technology described herein, formulation of DNA onto cationic poly(lactide-coglycolide) (PLG) microparticles, has been developed as a means to better target DNA to antigen-presenting cells (APCs). PLG microparticles are an attractive approach for vaccine delivery, since the polymer is biodegradable and biocompatible and has been used to develop several drug delivery systems (21). In addition, PLG microparticles have also been used for a number of years as delivery systems for entrapped vaccine antigens (24). More recently, PLG microparticles have been described as a delivery system for entrapped DNA vaccines (15,18). Nevertheless, recent observations have shown that DNA is damaged during microencapsulation, leading to a significant reduction in supercoiled DNA (2, 29). Moreover, the encapsulation efficiency is often low. Therefore, we developed a novel approach of adsorbing DNA onto the surface of PLG microparticles to avoid the problems associated with microencapsulation of DNA. This approach, ...

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Properties of a baboon lymphotropic herpesvirus related to Epstein‐Barr virus

Cited by 115 publications

References 21 publications

Evolutionary Conservation of Primate Lymphocryptovirus MicroRNA Targets

Evolutionary Conservation of Primate Lymphocryptovirus MicroRNA Targets

Increased Expression and Immunogenicity of Sequence-Modified Human Immunodeficiency Virus Type 1 gag Gene

Induction of Potent Immune Responses by Cationic Microparticles with Adsorbed Human Immunodeficiency Virus DNA Vaccines

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