Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice

Stubbs, Sarah H.; Pontelli, Marjorie Cornejo; Mishra, Nischay; Zhou, Chunxia; Souza, Juliano de Paula; Viana, Rosa Maria Mendes; Lipkin, W. Ian; Knipe, David M.; Arruda, Eurico; Whelan, Sean P. J.

doi:10.1128/mbio.00463-21

Cited by 13 publications

(7 citation statements)

References 53 publications

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“…The PRVABC59 (Human/2015/Puerto Rico) strain of ZIKV was obtained from BEI Resources (NR-50240) from the Arbovirus Reference Collection (CDC, Fort Collins, CO, USA). VSV-OROV virus was generated as described previously ( 30 ). All of the viruses were propagated in Vero E6 cells with standard culture conditions using D2 media supplemented with 1% Pen/Strep and 1% l -Glut.…”

Section: Methodsmentioning

confidence: 99%

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Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1

Schwarz

Price

Ganaie

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Oropouche orthobunyavirus (OROV; Peribunyaviridae ) is a mosquito-transmitted virus that causes widespread human febrile illness in South America, with occasional progression to neurologic effects. Host factors mediating the cellular entry of OROV are undefined. Here, we show that OROV uses the host protein low-density lipoprotein–related protein 1 (Lrp1) for efficient cellular infection. Cells from evolutionarily distinct species lacking Lrp1 were less permissive to OROV infection than cells with Lrp1. Treatment of cells with either the high-affinity Lrp1 ligand receptor-associated protein (RAP) or recombinant ectodomain truncations of Lrp1 significantly reduced OROV infection. In addition, chimeric vesicular stomatitis virus (VSV) expressing OROV glycoproteins (VSV-OROV) bound to the Lrp1 ectodomain in vitro. Furthermore, we demonstrate the biological relevance of the OROV-Lrp1 interaction in a proof-of-concept mouse study in which treatment of mice with RAP at the time of infection reduced tissue viral load and promoted survival from an otherwise lethal infection. These results with OROV, along with the recent finding of Lrp1 as an entry factor for Rift Valley fever virus, highlight the broader significance of Lrp1 in cellular infection by diverse bunyaviruses. Shared strategies for entry, such as the critical function of Lrp1 defined here, provide a foundation for the development of pan-bunyaviral therapeutics.

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Section: Methodsmentioning

confidence: 99%

“…VSV-OROV was grown in BSR cells in DMEM media containing 2% FBS, as described previously ( 30 ). The supernatants containing the virus from two 150-mm dishes were collected, filtered, and concentrated by high-speed ultracentrifugation.…”

Section: Methodsmentioning

confidence: 99%

Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1

Schwarz

Price

Ganaie

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…The PRVABC59 (Human/2015/Puerto Rico) strain of ZIKV was obtained from BEI Resources (NR-50240) from the Arbovirus Reference Collection, CDC Fort Collins, CO, USA. VSV-OROV virus was generated as described previously (Stubbs et al, 2021). All viruses were propagated in Vero E6 cells (ATCC, CRL-1586) with standard culture conditions using D2 media supplemented with 1% Pen/Strep and 1% L-Glut.…”

Section: Methodsmentioning

confidence: 99%

Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1

Schwarz

Price

Ganaie

et al. 2022

Preprint

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Oropouche orthobunyavirus (OROV; Peribunyaviridae) is a mosquito-transmitted virus that causes widespread cases of human febrile illness in South America, with occasional progression to neurologic effects. Host entry factors mediating cellular entry of OROV are undefined. Here, we show that OROV requires the host protein low density lipoprotein-related protein 1 (Lrp1) for cellular infection. Cells from evolutionarily distinct species lacking Lrp1 were less permissive to OROV infection than cells with Lrp1. Treatment of cells with either the high-affinity Lrp1 ligand receptor-associated protein (RAP) or recombinant ectodomain truncations of Lrp1 significantly reduced OROV infection. Thus, Lrp1 is an important host factor required for infection of cells by OROV. Taken together with our results showing that Lrp1 is a newly identified receptor for Rift Valley fever virus (RVFV), Lrp1 may play a broader role in cellular infection by bunyaviruses.

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“…The study also showed that the vaccine induced a robust immune response, with high levels of neutralizing antibodies detected in all vaccinated individuals. Furthermore, a recent study also explored the use of a replication-competent vesicular stomatitis virus (VSV) expressing OROV glycoproteins as a potential vaccine candidate ( Stubbs et al., 2021 ). This candidate vaccine was shown to protect mice from wild-type challenge, demonstrating its potential for human use.…”

Section: Vaccine Developmentmentioning

confidence: 99%

Oropouche virus: A neglected global arboviral threat

Zhang,

Liu,

et al. 2024

Virus Research

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Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice

Cited by 13 publications

References 53 publications

Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1

Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1

Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1

Oropouche virus: A neglected global arboviral threat

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