Rabies virus antinucleoprotein antibody protects against rabies virus challenge in vivo and inhibits rabies virus replication in vitro.

ABSTRACT An antigenic double mutant of rabies virus (challenge virus standard [CVS] strain) was selected by successive use of two neutralizing antiglycoprotein monoclonal antibodies, both specific for antigenic site III. This mutant differed from the original virus strain by two amino acid substitutions in the ectodomain of the glycoprotein. The lysine in position 330 and the arginine in position 333 were replaced by asparagine and methionine, respectively. This double mutant was not pathogenic for adult mice. When injected intramuscularly into the forelimbs of adult mice, this virus could not penetrate the nervous system, either by the motor or by the sensory route, while respective single mutants infected motoneurons in the spinal cord and sensory neurons in the dorsal root ganglia. In vitro experiments showed that the double mutant was able to infect BHK cells, neuroblastoma cells, and freshly prepared embryonic motoneurons, albeit with a lower efficiency than the CVS strain. Upon further incubation at 37°C, the motoneurons became resistant to infection by the mutant while remaining permissive to CVS infection. These results suggest that rabies virus uses different types of receptors: a molecule which is ubiquitously expressed at the surface of continuous cell lines and which is recognized by both CVS and the double mutant and a neuron-specific molecule which is not recognized by the double mutant.

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Filociclovir Is a Potent In Vitro and In Vivo Inhibitor of Human Adenoviruses

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01299-20 ◽

2020 ◽

Vol 64 (11) ◽

Author(s):

Karoly Toth ◽

Islam T. M. Hussein ◽

Ann E. Tollefson ◽

Baoling Ying ◽

Jacqueline F. Spencer ◽

...

Keyword(s):

Body Weight ◽

Virus Replication ◽

Antiviral Drug ◽

Clinical Manifestations ◽

Body Weight Loss ◽

Human Adenovirus ◽

Clinical Safety ◽

Virus Challenge

ABSTRACT Human adenovirus (HAdV) infection is common in the general population and can cause a range of clinical manifestations, among which pneumonia and keratoconjunctivitis are the most common. Although HAdV infections are mostly self-limiting, infections in immunocompromised individuals can be severe. No antiviral drug has been approved for treating adenoviruses. Filociclovir (FCV) is a nucleoside analogue which has successfully completed phase I human clinical safety studies and is now being developed for treatment of human cytomegalovirus (HCMV)-related disease in immunocompromised patients. In this report, we show that FCV is a potent broad-spectrum inhibitor of HAdV types 4 to 8, with 50% effective concentrations (EC50s) ranging between 1.24 and 3.6 μM and a 50% cytotoxic concentration (CC50) of 100 to 150 μM in human foreskin fibroblasts (HFFs). We also show that the prophylactic oral administration of FCV (10 mg/kg of body weight) 1 day prior to virus challenge and then daily for 14 days to immunosuppressed Syrian hamsters infected intravenously with HAdV6 was sufficient to prevent morbidity and mortality. FCV also mitigated tissue damage and inhibited virus replication in the liver. The 10-mg/kg dose had similar effects even when the treatment was started on day 4 after virus challenge. Furthermore, FCV administered at the same dose after intranasal challenge with HAdV6 partially mitigated body weight loss but significantly reduced pathology and virus replication in the lung. These findings suggest that FCV could potentially be developed as a pan-adenoviral inhibitor.

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Towards plant resistance to viruses using protein-only RNase P

Nature Communications ◽

10.1038/s41467-021-21338-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Anthony Gobert ◽

Yifat Quan ◽

Mathilde Arrivé ◽

Florent Waltz ◽

Nathalie Da Silva ◽

...

Keyword(s):

Mosaic Virus ◽

Virus Replication ◽

Yield Loss ◽

Rnase P ◽

Plant Viruses ◽

Yellow Mosaic Virus ◽

Resistance To Viruses ◽

Target Plant

AbstractPlant viruses cause massive crop yield loss worldwide. Most plant viruses are RNA viruses, many of which contain a functional tRNA-like structure. RNase P has the enzymatic activity to catalyze the 5′ maturation of precursor tRNAs. It is also able to cleave tRNA-like structures. However, RNase P enzymes only accumulate in the nucleus, mitochondria, and chloroplasts rather than cytosol where virus replication takes place. Here, we report a biotechnology strategy based on the re-localization of plant protein-only RNase P to the cytosol (CytoRP) to target plant viruses tRNA-like structures and thus hamper virus replication. We demonstrate the cytosol localization of protein-only RNase P in Arabidopsis protoplasts. In addition, we provide in vitro evidences for CytoRP to cleave turnip yellow mosaic virus and oilseed rape mosaic virus. However, we observe varied in vivo results. The possible reasons have been discussed. Overall, the results provided here show the potential of using CytoRP for combating some plant viral diseases.

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420 Small interfering RNA(siRNA)-mediated inhibition of hepatitis C virus replication using bicistronic vector in vivo (cell line Huh-7) and in vitro

Journal of Hepatology ◽

10.1016/s0168-8278(05)81832-x ◽

2005 ◽

Vol 42 ◽

pp. 154 ◽

Cited By ~ 1

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Cell Line ◽

Virus Replication ◽

Small Interfering Rna ◽

Bicistronic Vector ◽

Interfering Rna

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Dominant-Negative FADD Rescues the In Vivo Fitness of a Cytomegalovirus Lacking an Antiapoptotic Viral Gene

Journal of Virology ◽

10.1128/jvi.01803-07 ◽

2007 ◽

Vol 82 (5) ◽

pp. 2056-2064 ◽

Cited By ~ 44

Author(s):

Luka Čičin-Šain ◽

Zsolt Ruzsics ◽

Juergen Podlech ◽

Ivan Bubić ◽

Carine Menard ◽

...

Keyword(s):

Virus Replication ◽

Control Cell ◽

Death Receptor ◽

Formal Proof ◽

Dominant Negative ◽

Viral Fitness ◽

Viral Gene ◽

Apoptosis Inhibition

ABSTRACT Genes that inhibit apoptosis have been described for many DNA viruses. Herpesviruses often contain even more than one gene to control cell death. Apoptosis inhibition by viral genes is postulated to contribute to viral fitness, although a formal proof is pending. To address this question, we studied the mouse cytomegalovirus (MCMV) protein M36, which binds to caspase-8 and blocks death receptor-induced apoptosis. The growth of MCMV recombinants lacking M36 (ΔM36) was attenuated in vitro and in vivo. In vitro, caspase inhibition by zVAD-fmk blocked apoptosis in ΔM36-infected macrophages and rescued the growth of the mutant. In vivo, ΔM36 infection foci in liver tissue contained significantly more apoptotic hepatocytes and Kupffer cells than did revertant virus foci, and apoptosis occurred during the early phase of virus replication prior to virion assembly. To further delineate the mode of M36 function, we replaced the M36 gene with a dominant-negative FADD (FADDDN) in an MCMV recombinant. FADDDN was expressed in cells infected with the recombinant and blocked the death-receptor pathway, replacing the antiapoptotic function of M36. Most importantly, FADDDN rescued ΔM36 virus replication, both in vitro and in vivo. These findings have identified the biological role of M36 and define apoptosis inhibition as a key determinant of viral fitness.

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The recently identified flavivirus Bamaga virus is transmitted horizontally by Culex mosquitoes and interferes with West Nile virus replication in vitro and transmission in vivo

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0006886 ◽

2018 ◽

Vol 12 (10) ◽

pp. e0006886 ◽

Cited By ~ 6

Author(s):

Agathe M. G. Colmant ◽

Sonja Hall-Mendelin ◽

Scott A. Ritchie ◽

Helle Bielefeldt-Ohmann ◽

Jessica J. Harrison ◽

...

Keyword(s):

West Nile Virus ◽

Virus Replication ◽

West Nile ◽

Culex Mosquitoes

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Effects of Defective Interfering Viruses on Virus Replication and Pathogenesis In Vitro and In Vivo

Advances in Virus Research - Advances in Virus Research Volume 40 ◽

10.1016/s0065-3527(08)60279-1 ◽

1991 ◽

pp. 181-211 ◽

Cited By ~ 144

Author(s):

Laurent Roux ◽

Anne E. Simon ◽

John J. Holland

Keyword(s):

Virus Replication

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Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus

Parasites & Vectors ◽

10.1186/s13071-019-3722-2 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

René G. P. van Gennip ◽

Barbara S. Drolet ◽

Paula Rozo Lopez ◽

Ashley J. C. Roost ◽

Jan Boonstra ◽

...

Keyword(s):

Virus Replication ◽

Bluetongue Virus ◽

Vector Competence ◽

Outer Shell ◽

Virus Propagation ◽

Virus Growth ◽

Shell Protein ◽

Vector Borne

Abstract Background Transmission of vector-borne virus by insects is a complex mechanism consisting of many different processes; viremia in the host, uptake, infection and dissemination in the vector, and delivery of virus during blood-feeding leading to infection of the susceptible host. Bluetongue virus (BTV) is the prototype vector-borne orbivirus (family Reoviridae). BTV serotypes 1–24 (typical BTVs) are transmitted by competent biting Culicoides midges and replicate in mammalian (BSR) and midge (KC) cells. Previously, we showed that genome segment 10 (S10) encoding NS3/NS3a protein is required for virus propagation in midges. BTV serotypes 25–27 (atypical BTVs) do not replicate in KC cells. Several distinct BTV26 genome segments cause this so-called ‘differential virus replication’ in vitro. Methods Virus strains were generated using reverse genetics and their growth was examined in vitro. The midge feeding model has been developed to study infection, replication and disseminations of virus in vivo. A laboratory colony of C. sonorensis, a known competent BTV vector, was fed or injected with BTV variants and propagation in the midge was examined using PCR testing. Crossing of the midgut infection barrier was examined by separate testing of midge heads and bodies. Results A 100 nl blood meal containing ±105.3 TCID50/ml of BTV11 which corresponds to ±20 TCID50 infected 50% of fully engorged midges, and is named one Midge Alimentary Infective Dose (MAID50). BTV11 with a small in-frame deletion in S10 infected blood-fed midge midguts but virus release from the midgut into the haemolymph was blocked. BTV11 with S1[VP1] of BTV26 could be adapted to virus growth in KC cells, and contained mutations subdivided into ‘corrections’ of the chimeric genome constellation and mutations associated with adaptation to KC cells. In particular one amino acid mutation in outer shell protein VP2 overcomes differential virus replication in vitro and in vivo. Conclusion Small changes in NS3/NS3a or in the outer shell protein VP2 strongly affect virus propagation in midges and thus vector competence. Therefore, spread of disease by competent Culicoides midges can strongly differ for very closely related viruses.

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