scholarly journals Recombination with Host Transgenes and Effects on Virus Evolution: An Overview and Opinion

1999 ◽  
Vol 12 (2) ◽  
pp. 87-92 ◽  
Author(s):  
Teresa Rubio ◽  
Marise Borja ◽  
Herman B. Scholthof ◽  
Andrew O. Jackson
Keyword(s):  
Coat Protein ◽  
Protein Gene ◽  
Virus Disease ◽  
Virus Evolution ◽  
Wild Type Virus ◽  
Negative Consequences ◽  
Wild Type ◽  
Sources Of Resistance ◽  
Double Recombination ◽  
Virus Mutant

This commentary relates to the work by M. Borja et al. (M. Borja, T. Rubio, H. B. Scholthof, and A. O. Jackson, MPMI 12:153-162, 1999) that shows that wild-type virus can be restored frequently by double recombination events between a tomato bushy stunt virus mutant with deletions inactivating the coat protein gene and a coat protein transgene. Here, we focus on evidence suggesting that new viruses might evolve via recombination with transgenes used for disease resistance, and discuss the potential effects of widespread use of these sources of resistance on virus evolution. We argue that the benefits arising from using transgenic sources of resistance for virus disease control outweigh potential negative consequences of evolution of novel hybrid viruses with destructive disease potential.

scholarly journals Restoration of Wild-Type Virus by Double Recombination of Tombusvirus Mutants with a Host Transgene

1999 ◽  
Vol 12 (2) ◽  
pp. 153-162 ◽  
Author(s):  
Marise Borja ◽  
Teresa Rubio ◽  
Herman B. Scholthof ◽  
Andrew O. Jackson
Keyword(s):  
Coat Protein ◽  
Transgenic Plants ◽  
Coat Protein Gene ◽  
Protein Gene ◽  
Wild Type Virus ◽  
Type Virus ◽  
Virus Infections ◽  
Wild Type ◽  
Transgenic Lines ◽  
Double Recombination

Nicotiana benthamiana plants transformed with the coat protein gene of tomato bushy stunt virus (TBSV) failed to elicit effective virus resistance when inoculated with wild-type virus. Subsequently, R1 and R2 progeny from 13 transgenic lines were inoculated with a TBSV mutant containing a defective coat protein gene. Mild symptoms typical of those elicited in nontransformed plants infected with the TBSV mutant initially appeared. However, within 2 to 4 weeks, up to 20% of the transgenic plants sporadically began to develop the lethal syndrome characteristic of wild-type virus infections. RNA hybridization and immunoblot analyses of these plants and nontransformed N. benthamiana inoculated with virus from the transgenic lines indicated that wild-type virus had been regenerated by a double recombination event between the defective virus and the coat protein transgene. Similar results were obtained with a TBSV deletion mutant containing a nucleotide sequence marker, and with a chimeric cucumber necrosis virus (CNV) containing the defective TBSV coat protein gene. In both cases, purified virions contained wild-type TBSV RNA or CNV chimeric RNA derived by recombination with the transgenic coat protein mRNA. These results thus demonstrate that recombinant tombusviruses can arise frequently from viral genes expressed in transgenic plants.

Plants Transformed with a Mutant Alfalfa Mosaic Virus Coat Protein Gene Are Resistant to the Mutant but Not to Wild-Type Virus

Virology ◽  
1994 ◽  
Vol 203 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Peter E.M. Taschner ◽  
Guido Van Marle ◽  
Frans Th. Brederode ◽  
Nilgun E. Tumer ◽  
John F. Bol
Keyword(s):  
Coat Protein ◽  
Mosaic Virus ◽  
Coat Protein Gene ◽  
Protein Gene ◽  
Alfalfa Mosaic Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Virus Coat Protein ◽  
Virus Coat

scholarly journals Production of Noncapped Genomic RNAs Is Critical to Sindbis Virus Disease and Pathogenicity

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Autumn T. LaPointe ◽  
V Douglas Landers ◽  
Claire E. Westcott ◽  
Kevin J. Sokoloski
Keyword(s):  
Sindbis Virus ◽  
Virus Disease ◽  
Severe Disease ◽  
Wild Type Virus ◽  
Wild Type ◽  
Genomic Rnas ◽  
Mortality And Morbidity ◽  
The Impact

ABSTRACT Alphaviruses are positive-sense RNA viruses that utilize a 5′ cap structure to facilitate translation of viral proteins and to protect the viral RNA genome. Nonetheless, significant quantities of viral genomic RNAs that lack a canonical 5′ cap structure are produced during alphaviral replication and packaged into viral particles. However, the role/impact of the noncapped genomic RNA (ncgRNA) during alphaviral infection in vivo has yet to be characterized. To determine the importance of the ncgRNA in vivo, the previously described D355A and N376A nsP1 mutations, which increase or decrease nsP1 capping activity, respectively, were incorporated into the neurovirulent AR86 strain of Sindbis virus to enable characterization of the impact of altered capping efficiency in a murine model of infection. Mice infected with the N376A nsP1 mutant exhibited slightly decreased rates of mortality and delayed weight loss and neurological symptoms, although levels of inflammation in the brain were similar to those of wild-type infection. Although the D355A mutation resulted in decreased antiviral gene expression and increased resistance to interferon in vitro, mice infected with the D355A mutant showed significantly reduced mortality and morbidity compared to mice infected with wild-type virus. Interestingly, expression of proinflammatory cytokines was found to be significantly decreased in mice infected with the D355A mutant, suggesting that capping efficiency and the production of ncgRNA are vital to eliciting pathogenic levels of inflammation. Collectively, these data indicate that the ncgRNA have important roles during alphaviral infection and suggest a novel mechanism by which noncapped viral RNAs aid in viral pathogenesis. IMPORTANCE Mosquito-transmitted alphaviruses have been the cause of widespread outbreaks of disease that can range from mild illness to lethal encephalitis or severe polyarthritis. There are currently no safe and effective vaccines or therapeutics with which to prevent or treat alphaviral disease, highlighting the need to better understand alphaviral pathogenesis to develop novel antiviral strategies. This report reveals production of noncapped genomic RNAs (ncgRNAs) to be a novel determinant of alphaviral virulence and offers insight into the importance of inflammation to pathogenesis. Taken together, the findings reported here suggest that the ncgRNAs contribute to alphaviral pathogenesis through the sensing of the ncgRNAs during alphaviral infection and are necessary for the development of severe disease.

scholarly journals Activity of the Oral Neuraminidase Inhibitor A-322278 against the Oseltamivir-Resistant H274Y (A/H1N1) Influenza Virus Mutant in Mice

2008 ◽  
Vol 53 (2) ◽  
pp. 791-793 ◽  
Author(s):  
Mariana Baz ◽  
Yacine Abed ◽  
Benjamin Nehmé ◽  
Guy Boivin
Keyword(s):  
Influenza A ◽  
Neuraminidase Inhibitor ◽  
H1n1 Influenza ◽  
Mortality Rates ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
H1n1 Influenza Virus ◽  
Influenza A H1n1 ◽  
Virus Mutant

ABSTRACT The new oral neuraminidase (NA) inhibitor A-322278 was evaluated in mice infected with influenza A/H1N1 wild-type virus or the oseltamivir-resistant (H274Y mutant) virus. A-322278 decreased mortality rates and lung virus titers significantly more than oseltamivir in mice infected with the NA H274Y mutant when therapy was started 4 h before or even 48 h after infection.

scholarly journals Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease

2015 ◽  
Vol 23 (3) ◽  
pp. 189-195 ◽  
Author(s):  
Patricio L. Acosta ◽  
Mauricio T. Caballero ◽  
Fernando P. Polack
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Disease ◽  
Wild Type Virus ◽  
Wild Type ◽  
T Helper ◽  
Vaccine Candidates ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Complex Deposition

ABSTRACTIn 1967, infants and toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (RSV) experienced an enhanced form of RSV disease characterized by high fever, bronchopneumonia, and wheezing when they became infected with wild-type virus in the community. Hospitalizations were frequent, and two immunized toddlers died upon infection with wild-type RSV. The enhanced disease was initially characterized as a “peribronchiolar monocytic infiltration with some excess in eosinophils.” Decades of research defined enhanced RSV disease (ERD) as the result of immunization with antigens not processed in the cytoplasm, resulting in a nonprotective antibody response and CD4+T helper priming in the absence of cytotoxic T lymphocytes. This response to vaccination led to a pathogenic Th2 memory response with eosinophil and immune complex deposition in the lungs after RSV infection. In recent years, the field of RSV experienced significant changes. Numerous vaccine candidates with novel designs and formulations are approaching clinical trials, defying our previous understanding of favorable parameters for ERD. This review provides a succinct analysis of these parameters and explores criteria for assessing the risk of ERD in new vaccine candidates.

scholarly journals The Poxvirus A35 Protein Is an Immunoregulator

2009 ◽  
Vol 84 (1) ◽  
pp. 418-425 ◽  
Author(s):  
Kristina E. Rehm ◽  
Gwendolyn J. B. Jones ◽  
Alice A. Tripp ◽  
Mark W. Metcalf ◽  
Rachel L. Roper
Keyword(s):  
Immune Response ◽  
Cytotoxic T Lymphocyte ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Lethal Challenge ◽  
Target Organs ◽  
Important Virulence Factor ◽  
Virus Mutant ◽  
Lymphocyte Responses

ABSTRACT It was shown previously that the highly conserved vaccinia virus A35 gene is an important virulence factor in respiratory infection of mice. We show here that A35 is also required for full virulence by the intraperitoneal route of infection. A virus mutant in which the A35 gene has been removed replicated normally and elicited improved antibody, gamma interferon-secreting cell, and cytotoxic T-lymphocyte responses compared to wild-type virus, suggesting that A35 increases poxvirus virulence by immunomodulation. The enhanced immune response correlated with an improved control of viral titers in target organs after the development of the specific immune response. Finally, the A35 deletion mutant virus also provided protection from lethal challenge (1,000 50% lethal doses) equal to that of the wild-type virus. Together, these data suggest that A35 deletion viruses will make safer and more efficacious vaccines for poxviruses. In addition, the A35 deletion viruses will serve as improved platform vectors for other infectious diseases and cancer and will be superior vaccine choices for postexposure poxvirus vaccination, as they also provide improved kinetics of the immune response.

scholarly journals Characterization of a Vaccinia Virus Mutant with a Deletion of the D10R Gene Encoding a Putative Negative Regulator of Gene Expression

2006 ◽  
Vol 80 (2) ◽  
pp. 553-561 ◽  
Author(s):  
Susan Parrish ◽  
Bernard Moss
Keyword(s):  
Vaccinia Virus ◽  
Deletion Mutant ◽  
Negative Regulator ◽  
Wild Type Virus ◽  
Wild Type ◽  
Gene Encoding ◽  
Early Proteins ◽  
Late Transcription ◽  
Infected Cells ◽  
Virus Mutant

ABSTRACT The D9 and D10 proteins of vaccinia virus are 25% identical to each other, contain a mutT motif characteristic of nudix hydrolases, and are conserved in all sequenced poxviruses. Previous studies indicated that overexpression of D10 and, to a lesser extent, D9 decreased the levels of capped mRNAs and their translation products. Here, we further characterized the D10 protein and showed that only trace amounts are associated with purified virions and that it is expressed exclusively at late times after vaccinia virus infection. A viable deletion mutant (vΔD10) produced smaller plaques and lower virus yields than either wild-type virus or a D9R deletion mutant (vΔD9). Purified vΔD10 virions appeared normal by microscopic examination and biochemical analysis but produced 6- to 10-fold-fewer plaques at the same concentration as wild-type or vΔD9 virions. When 4 PFU per cell of wild-type or vΔD9 virions or equal numbers of vΔD10 virions were used for inoculation, nearly all cells were infected in each case, but viral early and late transcription was initiated more slowly in vΔD10-infected cells than in the others. However, viral early transcripts accumulated to higher levels in vΔD10-infected cells than in cells infected with the wild type or vΔD9. In addition, viral early and late mRNAs and cellular actin mRNA persisted longer in vΔD10-infected cells than in others. Furthermore, analysis of pulse-labeled proteins indicated prolonged synthesis of cellular and viral early proteins. These results are consistent with a role for D10 in regulating RNA levels in poxvirus-infected cells.

scholarly journals Wheat streak mosaic virus Coat Protein Deletion Mutants Elicit More Severe Symptoms Than Wild-Type Virus in Multiple Cereal Hosts

2017 ◽  
Vol 30 (12) ◽  
pp. 974-983 ◽  
Author(s):  
Satyanarayana Tatineni ◽  
Christian Elowsky ◽  
Robert A. Graybosch
Keyword(s):  
Amino Acids ◽  
Coat Protein ◽  
Mosaic Virus ◽  
Wheat Streak Mosaic Virus ◽  
Wild Type Virus ◽  
Deletion Mutants ◽  
Major Protein ◽  
Type Virus ◽  
Wild Type ◽  
Genomic Rnas

Previously, we reported that coat protein (CP) of Wheat streak mosaic virus (WSMV) (genus Tritimovirus, family Potyviridae) tolerates deletion of amino acids 36 to 84 for efficient systemic infection of wheat. In this study, we demonstrated that WSMV mutants with deletion of CP amino acids 58 to 84 but not of 36 to 57 induced severe chlorotic streaks and spots, followed by acute chlorosis in wheat, maize, barley, and rye compared with mild to moderate chlorotic streaks and mosaic symptoms by wild-type virus. Deletion of CP amino acids 58 to 84 from the WSMV genome accelerated cell-to-cell movement, with increased accumulation of genomic RNAs and CP, compared with the wild-type virus. Microscopic examination of wheat tissues infected by green fluorescent protein–tagged mutants revealed that infection by mutants lacking CP amino acids 58 to 84 caused degradation of chloroplasts, resulting in acute macroscopic chlorosis. The profile of CP-specific proteins was altered in wheat infected by mutants causing acute chlorosis, compared with mutants eliciting wild-type symptoms. All deletion mutants accumulated CP-specific major protein similarly to that in wild-type virus; however, mutants that elicit acute chlorosis failed to accumulate a 31-kDa minor protein compared with wild-type virus or mutants lacking amino acids 36 to 57. Taken together, these data suggest that deletion of CP amino acids 58 to 84 from the WSMV genome enhanced accumulation of CP and genomic RNA, altered CP-specific protein profiles, and caused severe symptom phenotypes in multiple cereal hosts.

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