Host Influence on the Characteristics of Venezuelan Equine Encephalomyelitis Virus

Heydrick, Fred P.; Wachter, Ralph F.; Hearn, Henry J.; ., Jr.

doi:10.21236/ad0475577

Cited by 5 publications

(7 citation statements)

References 3 publications

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“…The lipids of Sindbis virus have been analyzed for their polar groups [5,9], and those of Semliki Forest virus (SFV) for both their polar groups and their fatty chains [7,10,11 ]. The viral lipids seem to vary considerably depending on the host cells [12]. As a complement to the earlier studies, we now report the overall chemical composition and the carbohydrate composition of SFV grown in BHK21 cells.…”

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confidence: 72%

Chemical Composition of Semliki Forest Virus

Laine

Söderlund

Renkonen³

1973

Intervirology

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Chemical analysis of Semliki Forest virus grown in BHK21 cells revealed 6.3 % RNA, 12.2 % nucleocapsid protein, 44.4 % envelope polypeptides, 30.8 % lipid and 6.3 % proteinbound carbohydrate. The monosaccharides found in the virus include N-acetyl-glucosamine, N-acetyl-galactosamine, mannose, galactose, glucose, fucose and sialic acid. Analyses of the individual monosaccharides are presented. The number of molecules of each of the major constituents in an average virion was calculated.

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confidence: 72%

Chemical Composition of Semliki Forest Virus

Laine

Söderlund

Renkonen³

1973

Intervirology

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“…Alphavirus variants with reduced plaque sizes often have reduced virulence in vivo as well, although there are certainly exceptions to this rule, and fresh wild-type isolates frequently contain a mixture of large-plaque and small-plaque viruses. Repeated tissue culture passaging of alphaviruses can lead to decreased plaque size and decreased virulence (19,39). Small-plaque and largeplaque alphavirus variants typically have different affinities for hydroxyapatite (a form of calcium phosphate), indicating changes in the surface charge of the glycoproteins (3,23).…”

Section: Discussionmentioning

confidence: 99%

Binding of Sindbis Virus to Cell Surface Heparan Sulfate

Byrnes¹,

Griffin

1998

J Virol

262

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Alphaviruses are arthropod-borne viruses with wide species ranges and diverse tissue tropisms. The cell surface receptors which allow infection of so many different species and cell types are still incompletely characterized. We show here that the widely expressed glycosaminoglycan heparan sulfate can participate in the binding of Sindbis virus to cells. Enzymatic removal of heparan sulfate or the use of heparan sulfate-deficient cells led to a large reduction in virus binding. Sindbis virus bound to immobilized heparin, and this interaction was blocked by neutralizing antibodies against the viral E2 glycoprotein. Further experiments showed that a high degree of sulfation was critical for the ability of heparin to bind Sindbis virus. However, Sindbis virus was still able to infect and replicate on cells which were completely deficient in heparan sulfate, indicating that additional receptors must be involved. Cell surface binding of another alphavirus, Ross River virus, was found to be independent of heparan sulfate.

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“…Although in vitro assessment of virus inactivation on BHK cell monolayers is a sensitive test, intracerebral (IC) inoculation of newborn mice was shown to have a greater degree of sensitivity for detection of latent neurotropic viruses (Heydrick et al, 1966). This procedure is routinely used for adventitious agent testing of biologic products and has been considered the “gold standard” for assessing inactivation/attenuation of VEEV (Sharma et al, 2007).…”

Section: 0 Experimental/materials and Methodsmentioning

confidence: 99%

A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV)

Fine¹,

Jenkins²,

Martin³

et al. 2010

Journal of Virological Methods

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A multisystem approach was used to assess the efficiency of several methods for inactivation of Venezuelan equine encephalitis virus (VEEV) vaccine candidates. A combination of diverse assays (plaque, in vitro cytopathology and mouse neurovirulence) was used to verify virus inactivation, along with the use of a specific ELISA to measure retention of VEEV envelope glycoprotein epitopes in the development of several inactivated VEEV candidate vaccines derived from an attenuated strain of VEEV (V3526). Incubation of V3526 aliquots at temperatures in excess of 64°C for periods >30 minutes inactivated the virus, but substantially reduced VEEV specific monoclonal antibody binding of the inactivated material. In contrast, V3526 treated either with formalin at concentrations of 0.1% or 0.5% v/v for 4 or 24 hours, or irradiated with 50 kilogray gamma radiation rendered the virus noninfectious while retaining significant levels of monoclonal antibody binding. Loss of infectivity of both the formalin inactivated (fV3526) and gamma irradiated (gV3526) preparations was confirmed via five successive blind passages on BHK-21 cells. Similarly, loss of neurovirulence for fV3526 and gV3526 was demonstrated via intracerebral inoculation of suckling BALB/c mice. Excellent protection against subcutaneous challenge with VEEV IA/B Trinidad donkey strain was demonstrated using a two dose immunization regimen with either fV3526 or gV3526. The combination of in vitro and in vivo assays provides a practical approach to optimize manufacturing process parameters for development of other inactivated viral vaccines. KeywordsVenezuelan equine encephalitis virus (VEEV); Formalin inactivated vaccines; Gamma irradiated vaccines; Neurovirulence; Alphavirus Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript IntroductionOver the past eighty years Venezuelan equine encephalitis virus (VEEV), an alphavirus (family Togaviridae) transmitted by mosquitoes, has caused periodic outbreaks of febrile and neurological disease in equine and human populations in Central and South America, as well as North America (Mexico and Texas) [Weaver et al., 2004]. Due to its highly infectious nature by aerosol [de Mucha-Macias and Sanchez-Spindola, 1965;Dietz et al., 1979], VEEV is also considered a potential biological weapon amenable to use in warfare and terrorism (Smith et al., 1997;Weaver et al., 2004). To address the above health concerns, two vaccines were developed by the U.S. government during the 1960s and 1970s: TC-83 (McKi...

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Host Influence on the Characteristics of Venezuelan Equine Encephalomyelitis Virus

Cited by 5 publications

References 3 publications

Chemical Composition of Semliki Forest Virus

Chemical Composition of Semliki Forest Virus

Binding of Sindbis Virus to Cell Surface Heparan Sulfate

A multisystem approach for development and evaluation of inactivated vaccines for Venezuelan equine encephalitis virus (VEEV)

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