Increased LAMP1 Expression Enhances SARS-CoV-1 and SARS-CoV-2 Production in Vero-Derived Transgenic Cell Lines

Dolskiy, Alexander A.; Grishchenko, I. V.; Боднев, С. А.; Nazarenko, A. A.; Smirnova, Anastasia M.; Matveeva, Anna K.; Le, Bulychev; Ovchinnikova, A. S.; Трегубчак, Т. В.; Zaykovskaya, А. V.; Imatdinov, Ilnaz; Pyankov, Oleg V.; Gavrilova, Elena V.; Agafonov, A. P.; Yudkin, Dmitry V.

doi:10.1134/s0026893322030050

Cited by 2 publications

(2 citation statements)

References 23 publications

(26 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5 ) at 48 hpi could be an innate immune response to abrogate viral replication and release. The significant downregulation of LAMP1 observed at 48 hpi in Deer-RECs further supports this, which is in line with a previous study reporting that an increase in the expression of the LAMP1 gene promoted SARS-CoV-2 production via exocytosis in Vero cells ( 51 ).…”

Section: Discussionsupporting

confidence: 91%

How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

Sarlo Davila,

Nelli,

Phadke

et al. 2024

Microbiol Spectr

View full text Add to dashboard Cite

The potential infectivity of severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) in animals raises a public health and economic concern, particularly the high susceptibility of white-tailed deer (WTD) to SARS-CoV-2. The disparity in the disease outcome between humans and WTD is very intriguing, as the latter are often asymptomatic, subclinical carriers of SARS-CoV-2. To date, no studies have evaluated the innate immune factors responsible for the contrasting SARS-CoV-2-associated disease outcomes in these mammalian species. A comparative transcriptomic analysis in primary respiratory epithelial cells of human (HRECs) and WTD (Deer-RECs) infected with the SARS-CoV-2 WA1/2020 strain was assessed throughout 48 h post inoculation (hpi). Both HRECs and Deer-RECs were susceptible to virus infection, with significantly ( P < 0.001) lower virus replication in Deer-RECs. The number of differentially expressed genes (DEG) gradually increased in Deer-RECs but decreased in HRECs throughout the infection. The ingenuity pathway analysis of DEGs further identified that genes commonly altered during SARS-CoV-2 infection mainly belong to cytokine and chemokine response pathways mediated via interleukin-17 (IL-17) and nuclear factor-κB (NF-κB) signaling pathways. Inhibition of the NF-κB signaling in the Deer-RECs pathway was predicted as early as 6 hpi. The findings from this study could explain the lack of clinical signs reported in WTD in response to SARS-CoV-2 infection as opposed to the severe clinical outcomes reported in humans. IMPORTANCE This study demonstrated that human and white-tailed deer primary respiratory epithelial cells are susceptible to the SARS-CoV-2 WA1/2020 strain infection. However, the comparative transcriptomic analysis revealed that deer cells could limit viral replication without causing hypercytokinemia by downregulating IL-17 and NF-κB signaling pathways. Identifying differentially expressed genes in human and deer cells that modulate key innate immunity pathways during the early infection will lead to developing targeted therapies toward preventing or mitigating the “cytokine storm” often associated with severe cases of coronavirus disease 19 (COVID-19). Moreover, results from this study will aid in identifying novel prognostic biomarkers in predicting SARS-CoV-2 adaption and transmission in deer and associated cervids.

show abstract

Section: Discussionsupporting

confidence: 91%

How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

Sarlo Davila,

Nelli,

Phadke

et al. 2024

Microbiol Spectr

View full text Add to dashboard Cite

show abstract

“…The copyright holder for this preprint (which this version posted April 25, 2023. ; https://doi.org/10.1101/2023.04.24.538130 doi: bioRxiv preprint 15 study reporting that an increase in the expression of the LAMP1 gene promoted SARS-CoV-2 production via exocytosis in Vero cells 52 .…”

Section: Deer-recsmentioning

confidence: 99%

How Do Deer Respiratory Epithelial Cells Weather The Initial Storm of SARS-CoV-2?

Davila

Nelli

Phadke

et al. 2023

Preprint

View full text Add to dashboard Cite

The potential infectivity of SARS-CoV-2 in animals raises a public health and economic concern, particularly the high susceptibility of white-tailed deer (WTD) to SARS-CoV-2. The disparity in the disease outcome between humans and WTD is very intriguing, as the latter are often asymptomatic, subclinical carriers of SARS-CoV-2. To date, no studies have evaluated the innate immune factors responsible for the contrasting SARS-CoV-2-associated disease outcomes in these mammalian species. A comparative transcriptomic analysis in primary respiratory epithelial cells of human (HRECs) and WTD (Deer-RECs) infected with SARS-CoV-2 was assessed throughout 48 hours post inoculation (hpi). Both HRECs and Deer-RECs were susceptible to SARS-COV-2, with significantly (P < 0.001) lower virus replication in Deer-RECs. The number of differentially expressed genes (DEG) gradually increased in Deer-RECs but decreased in HRECs throughout the infection. The ingenuity pathway analysis of DEGs further identified that genes commonly altered during SARS-CoV-2 infection mainly belong to cytokine and chemokine response pathways mediated via IL-17 and NF-κB signaling pathways. Inhibition of the NF-κB signaling in the Deer-RECs pathway was predicted as early as 6 hpi. The findings from this study could explain the lack of clinical signs reported in WTD in response to SARS-CoV-2 infection as opposed to the severe clinical outcomes reported in humans.

show abstract

Increased LAMP1 Expression Enhances SARS-CoV-1 and SARS-CoV-2 Production in Vero-Derived Transgenic Cell Lines

Cited by 2 publications

References 23 publications

How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

How do deer respiratory epithelial cells weather the initial storm of SARS-CoV-2 WA1/2020 strain?

How Do Deer Respiratory Epithelial Cells Weather The Initial Storm of SARS-CoV-2?

Contact Info

Product

Resources

About