Robust dengue virus infection in bat cells and limited innate immune responses coupled with positive serology from bats in IndoMalaya and Australasia

Irving, Aaron T.; Rozario, Pritisha; Kong, Pui San; Luko, Katarina; Gorman, Jeffrey J.; Hastie, Marcus L.; Chia, Wan Ni; Mani, Shailendra; Lee, Benjamin Py H.; Smith, Gavin; Mendenhall, Ian H.; Larman, H. Benjamin; Elledge, Stephen J.; Wang, Lin‐Fa

doi:10.1007/s00018-019-03242-x

Cited by 15 publications

(13 citation statements)

References 72 publications

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“…To confirm IRF overexpression was not working by compensatory induction of IFNg/l, we treated the same cells with the Jak inhibitor ruxolitinib. Control and IFN-a3-stimulated cells showed a similar absence of IRG-induction profiles, as measured by a previously described nanostring panel (Irving et al, 2020), whereas ruxolitinib-treated cells with IFNa3 showed a slight increase, possibly indicating a degree of interference from IFNAR1 binding in the absence of IFNAR2. Fitting with the idea of Jak-STAT-signaling-independent, direct/indirect IRFdependent induction, ruxolitinib actually enhanced IRF-overexpression-induced IRG induction, particularly with genes such Cell Reports 33, 108345, November 3, 2020 5 Article ll OPEN ACCESS as XAF1, ZBP1, TLR6, RTP4, OASL, NLRC5, MX2, IFIT2/3, CXCL10, CIITA, and APOBEC3G (Figure S2I).…”

Section: Irf1 and Irf7 Regulate Antiviral Genes Basallysupporting

confidence: 79%

Interferon Regulatory Factors IRF1 and IRF7 Directly Regulate Gene Expression in Bats in Response to Viral Infection

et al. 2020

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Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNa) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.

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Section: Irf1 and Irf7 Regulate Antiviral Genes Basallysupporting

confidence: 79%

Interferon Regulatory Factors IRF1 and IRF7 Directly Regulate Gene Expression in Bats in Response to Viral Infection

et al. 2020

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“… [ 57 ] Bats Costa Rica Puntarenas & Liberia Urban/rural 1998 12/53 (22.6); D1,2 PRNT; Tested for D1/2/3/4 Active outbreaks of dengue, all 4 serotypes have be isolated in the past 6 years of the study. [ 49 ] Ecuador Tena 3/10 (30); D2,3 Unknown Bats Mexico Cuitzmala River Basin, Jalisco Forest 2014 0/83 (Tested against flavivirus; NS5) DENV reported in humans [ 59 ] Bats Brazil São Jose ´ do Rio Preto, São Paulo State Urban/rural 2014–2017 0/64 (Tested against flavivirus; NS5) 0/46 HI; Tested for D1/2/3/4 High incidence of arbovirus infection in humans [ 50 ] Barreiras, Bahia State 0/39 (Tested against flavivirus; NS5) 0/27 Known occurrences of DENV Bats Columbia San Carlos & Ayapel , Córdoba & Sucre Urban/rural Before 2019 2/286 (0.7); D2 (NS5)* [ 45 ] Bats Singapore Unknown Urban/rural Before 2019 14/106 (13.2); D2 (NS1) Luciferase LIPS; Tested for D2 NS1 antigen only [ 54 ] Bats Australia Townsville, Northern Queensland Urban/rural 1954 4/17 (23.5); D1 Mouse protection test; Tested for D1 only Extensive epidemic from Dec 1953 – Mar 1954, sporadic cases from Dec 1954 – Nov 1955. …”

Section: Resultsmentioning

confidence: 99%

“…Among the urban/rural setting where bats were captured, there were 13.1% (136/1036) of bats that were dengue positive by serology while no bats (0/91) captured in the forest setting was positive by serology ( p < 0.05). There were 14 studies involving the urban/rural setting [ [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] ], 4 involving the forest setting [ 44 , 52 , 58 , 59 ]. Of which, 12 and 2 studies respectively were based in those settings exclusively.…”

Section: Resultsmentioning

confidence: 99%

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Animals as potential reservoirs for dengue transmission: A systematic review

et al. 2021

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Dengue is a rapidly spreading mosquito-borne flavivirus infection that is prevalent in tropical and sub-tropical regions. Humans are known to be the main reservoir host maintaining the epidemic cycles of dengue but it is unclear if dengue virus is also maintained in a similar enzootic cycle. The systematic review was conducted in accordance to Cochrane's PRISMA recommendations. A search was done on PubMed, EMBASE, Scopus and Cochrane Library. Key data on animal dengue positivity was extracted and classified according to animal type and diagnostic modes. Of the 3818 articles identified, 56 articles were used in this review. A total of 16,333 animals were tested, 1817 of which were positive for dengue virus by RT-PCR or serology. Dengue positivity was detected in bats (10.1%), non-human primates (27.3%), birds (11%), bovid (4.1%), dogs (1.6%), horses (5.1%), pigs (34.1%), rodents (3.5%), marsupials (13%) and other small animals (7.3%). While majority of dengue positivity via serology suggests potential enzootic transmission, but regular dengue virus spillback cannot be excluded. With the exception of bats, acute infection among animals is limited. Further investigation on animals is critically required to better understand their role as potential reservoir in dengue transmission.

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“…The suppression of RIG-I signaling and caspase/cell-death pathways was observed in P . alecto kidney cell line (PaKiT03) during NBV infection [ 54 – 56 ]. RIG-I signaling might be the main mechanism for bats to avoid diseases after infection with PRV50G and other RNA viruses.…”

Section: Discussionmentioning

confidence: 99%

Distinct interferon response in bat and other mammalian cell lines infected with Pteropine orthoreovirus

et al. 2021

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Bats serve as natural hosts of Pteropine orthoreovirus (PRV), an emerging group of bat-borne, zoonotic viruses. Bats appear to possess unique innate immune system responses that can inhibit viral replication, thus reducing clinical symptoms. We examined the innate immune response against PRV and assessed viral replication in cell lines derived from four bat species ( Miniopterus fuliginosus , Pteropus dasymallus , Rhinolophus ferrumequinum , and Rousettus leschenaultii ), one rodent ( Mesocricetous auratus ), and human ( Homo sapiens ). The expression levels of pattern recognition receptors (PRRs) ( TLR3 , RIG-I , and MDA5 ) and interferons ( IFNB1 and IFNL1 ) were higher and PRV replication was lower in cell lines derived from M. fuliginosus , R. ferrumequinum , and R. leschenaultii . Reduction of IFNB1 expression by the knockdown of PRRs in the cell line derived from R. ferrumequinum was associated with increased PRV replication. The knockdown of RIG-I led to the most significant reduction in viral replication for all cell lines. These results suggest that RIG-I production is important for antiviral response against PRV in R. ferrumequinum . Supplementary Information The online version contains supplementary material available at 10.1007/s11262-021-01865-6.

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Robust dengue virus infection in bat cells and limited innate immune responses coupled with positive serology from bats in IndoMalaya and Australasia

Cited by 15 publications

References 72 publications

Interferon Regulatory Factors IRF1 and IRF7 Directly Regulate Gene Expression in Bats in Response to Viral Infection

Interferon Regulatory Factors IRF1 and IRF7 Directly Regulate Gene Expression in Bats in Response to Viral Infection

Animals as potential reservoirs for dengue transmission: A systematic review

Distinct interferon response in bat and other mammalian cell lines infected with Pteropine orthoreovirus

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