Increased Clinical Signs and Mortality in IFNAR(−/−) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype

Attoui, Houssam; Jaafar, Fauziah Mohd; Monsion, Baptiste; Klonjkowski, Bernard; Reid, Elizabeth; Fay, Petra C.; Saunders, Keith; Lomonossoff, George P.; Haig, David M.; Mertens, Peter P. C.

doi:10.3390/pathogens12040602

Cited by 5 publications

(5 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Globally speaking, the absence of detectable KEMV RNA in the older males’ hearts and the higher Ct values in the other tested organs of these older males strongly suggest an intriguing lower susceptibility of these animals. We have previously shown that attenuation of virulence of a BTV generated by reverse genetics correlated with lower levels of replication in IFNAR (−/−) mice, as observed by higher Ct values, regardless of the sex of the mice [ 22 ]. The Ct values of mice inoculated with KEMV Ps.BSR30 clearly indicate that there was an attenuation of virulence.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Age- and Sex-Associated Pathogenesis of Cell Culture-Passaged Kemerovo Virus in IFNAR(−/−) Mice

Migné,

Heckmann,

Monsion

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

Kemerovo virus (KEMV) is a tick-borne orbivirus transmitted by ticks of the genus Ixodes. Previous animal experimentation studies with orbiviruses, in particular the interferon receptor double knock-out (IFNAR(−/−)) mouse model, did not indicate bias that is related to age or sex. We endeavoured to assess the effect of serial and alternated passages of KEMV in mammalian or Ixodes cells on virus replication and potential virulence in male or female IFNAR(−/−) mice, with important age differences: younger males (4–5 months old), older males (14–15 months old), and old females (14–15 months old). After 30 serial passages in mammalian or tick cells, or alternated passages in the two cell types, older female mice which were inoculated with the resulting virus strains were the first to show clinical signs and die. Younger males behaved differently from older males whether they were inoculated with the parental strain of KEMV or with any of the cell culture-passaged strains. The groups of male and female mice inoculated with the mammalian cell culture-adapted KEMV showed the lowest viraemia. While older female and younger male mice died by day 6 post-inoculation, surprisingly, the older males survived until the end of the experiment, which lasted 10 days. RNA extracted from blood and organs of the various mice was tested by probe-based KEMV real-time RT-PCR. Ct values of the RNA extracts were comparable between older females and younger males, while the values for older males were >5 Ct units higher for the various organs, indicating lower levels of replication. It is noteworthy that the hearts of the old males were the only organs that were negative for KEMV RNA. These results suggest, for the first time, an intriguing age- and sex-related bias for an orbivirus in this animal model. Changes in the amino acid sequence of the RNA-dependent RNA polymerase of Kemerovo virus, derived from the first serial passage in Ixodes cells (KEMV Ps.IRE1), were identified in the vicinity of the active polymerase site. This finding suggests that selection of a subpopulation of KEMV with better replication fitness in tick cells occurred.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Vertrel XF (Sigma-Aldrich, Saint-Quentin-Fallavier, France) is an organic solvent that facilitates freeing orbivirus particles from interaction with cell debris [ 22 , 34 ]. On day 6 post-infection, BSR cell lysates, including cell debris and culture supernatants, were collected.…”

Section: Methodsmentioning

confidence: 99%

Age- and Sex-Associated Pathogenesis of Cell Culture-Passaged Kemerovo Virus in IFNAR(−/−) Mice

Migné,

Heckmann,

Monsion

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…We initially assessed the virulence of our BTV-1RG C7 using 10, 100 or 1000 pfu/mouse in 3 groups of 5 IFNAR (-/-) mice. Although clinical signs were observed by day 4, all mice recovered by day 6–7 [ 51 ], showing that BTV-1RG C7 is not as virulent as other BTV strains tested in this model [ 36 , 47 , 48 ]. Two groups of 5 IFNAR (-/-) mice each were used to compare the effects of infection with either BTV-1RG C7 or BTV-1∆NS4.…”

Section: Methodsmentioning

confidence: 99%

Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses

Mohd Jaafar,

Belhouchet,

Monsion

et al. 2023

Viruses

Self Cite

View full text Add to dashboard Cite

Non-structural protein 4 (NS4) of insect-borne and tick-borne orbiviruses is encoded by genome segment 9, from a secondary open reading frame. Though a protein dispensable for bluetongue virus (BTV) replication, it has been shown to counter the interferon response in cells infected with BTV or African horse sickness virus. We further explored the functional role(s) of NS4 proteins of BTV and the tick-borne Great Island virus (GIV). We show that NS4 of BTV or GIV helps an E3L deletion mutant of vaccinia virus to replicate efficiently in interferon-treated cells, further confirming the role of NS4 as an interferon antagonist. Our results indicate that ectopically expressed NS4 of BTV localised with caspase 3 within the nucleus and was found in a protein complex with active caspase 3 in a pull-down assay. Previous studies have shown that pro-apoptotic caspases (including caspase 3) suppress type I interferon response by cleaving mediators involved in interferon signalling. Our data suggest that orbivirus NS4 plays a role in modulating the apoptotic process and/or regulating the interferon response in mammalian cells, thus acting as a virulence factor in pathogenesis.

show abstract

“…Bluetongue virus (BTV) belongs to the Orbivirus genus of the Reoviridae family, characterized by a double-stranded RNA genome with 10 segments coding for various proteins. Currently, at least 36 different BTV serotypes are circulating worldwide [ 2 – 4 ].…”

Section: Introductionmentioning

confidence: 99%

First molecular evidence of potential Culicoides vectors implicated in bluetongue virus transmission in Morocco

Daif,

El Berbri,

Fassi Fihri

2024

Parasites Vectors

View full text Add to dashboard Cite

Background Bluetongue is a non-contagious viral disease that affects both domestic and wild ruminants. It is transmitted primarily by small hematophagous Diptera belonging to the genus Culicoides (Diptera: Ceratopogonidae). The current study represents the first molecular investigation into the potential role of Culicoides imicola, Culicoides paolae, Culicoides newsteadi, Culicoides spp., and Culicoides circumscriptus as bluetongue virus (BTV) vectors in Morocco. Additionally, the study aimed to evaluate the vectorial activity of midges during the survey seasons. Methods Parous females of these species were captured from several regions of Morocco (6 out of 12) from 2018 to 2021 using Onderstepoort Veterinary Institute (OVI) traps. A total of 2003 parous female specimens were grouped into 55 batches. The midge body of each batch was dissected into three regions (head, thorax, and abdomen), and these regions were analyzed separately using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results BTV RNA was detected in 45 out of the 55 batches tested, indicating a positivity rate of 81.8%. The RT-qPCR-positive pools of the studied Culicoides species exhibited high levels of BTV positivity in each body part (head, thorax, and abdomen), confirming the successful replication of the virus within midge bodies. The BTV circulation was substantial across all three survey seasons (spring, summer, and autumn). High infection rates, calculated using the minimum infection rate (MIR) and maximum likelihood estimation (MLE), were observed during the collection seasons, particularly in autumn and spring, and for all investigated Culicoides species, most notably for C. imicola and C. newsteadi. These increased infection rates underscore the significant risk of Culicoides transmitting the BTV in Morocco. Conclusions The detection of BTV positivity in Culicoides spp. (lacking wing spots that allow their differentiation according to morphological identification keys) suggested that other Culicoides species are competent for BTV transmission in Morocco. The study results indicated, for the first time at the molecular level, that C. imicola and C. newsteadi are the primary potential vectors of BTV in Morocco and that C. paolae and C. circumscriptus are strongly implicated in the propagation of bluetongue at the national level. Graphical Abstract

show abstract

Increased Clinical Signs and Mortality in IFNAR(−/−) Mice Immunised with the Bluetongue Virus Outer-Capsid Proteins VP2 or VP5, after Challenge with an Attenuated Heterologous Serotype

Cited by 5 publications

References 52 publications

Age- and Sex-Associated Pathogenesis of Cell Culture-Passaged Kemerovo Virus in IFNAR(−/−) Mice

Age- and Sex-Associated Pathogenesis of Cell Culture-Passaged Kemerovo Virus in IFNAR(−/−) Mice

Orbivirus NS4 Proteins Play Multiple Roles to Dampen Cellular Responses

First molecular evidence of potential Culicoides vectors implicated in bluetongue virus transmission in Morocco

Contact Info

Product

Resources

About