Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset


The development of vaccines and treatment strategies is aided by robust animal disease models that accurately depict the illness that is observed in humans. Here we describe a new, improved model for MERS-CoV using the common marmoset, whereby the severe, and even lethal, illness that has been observed in many human cases is recapitulated. Prior to the development of this model, the only available animal models for MERS-CoV infection were the rhesus macaque and a mouse model that requires adenovirus-transduced expression of the human version of the protein required for virus entry. The rhesus macaque model more closely mimics the mild to moderate disease observed in some patients—mainly those without significant comorbidities. The increased severity of illness in the common marmoset model is an important advance in the ability to evaluate potential therapeutic agents against MERS-CoV, as discrimination between successfully treated and control animals should be more apparent. In addition, the closer models recapitulate the disease observed in humans, the more likely findings can be eventually translated into use in humans.


Vyšlo v časopise: Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004250
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004250

Souhrn

The development of vaccines and treatment strategies is aided by robust animal disease models that accurately depict the illness that is observed in humans. Here we describe a new, improved model for MERS-CoV using the common marmoset, whereby the severe, and even lethal, illness that has been observed in many human cases is recapitulated. Prior to the development of this model, the only available animal models for MERS-CoV infection were the rhesus macaque and a mouse model that requires adenovirus-transduced expression of the human version of the protein required for virus entry. The rhesus macaque model more closely mimics the mild to moderate disease observed in some patients—mainly those without significant comorbidities. The increased severity of illness in the common marmoset model is an important advance in the ability to evaluate potential therapeutic agents against MERS-CoV, as discrimination between successfully treated and control animals should be more apparent. In addition, the closer models recapitulate the disease observed in humans, the more likely findings can be eventually translated into use in humans.


Zdroje

1. ProMED-mail (2014) MERS-CoV (05): Saudi Arabia, UAE, WHO, RFI.

2. HaagmansBL, Al DhahirySH, ReuskenCB, RajVS, GalianoM, et al. (2013) Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis 14: 140–5.

3. PereraRA, WangP, GomaaMR, El-SheshenyR, KandeilA, et al. (2013) Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill 18: pii = 20574.

4. ReuskenCB, HaagmansBL, MullerMA, GutierrezC, GodekeGJ, et al. (2013) Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis 13: 859–866.

5. BrieseT, MishraN, JainK, ZalmoutIS, JabadoOJ, et al. (2014) Middle East Respiratory Syndrome Coronavirus Quasispecies That Include Homologues of Human Isolates Revealed through Whole-Genome Analysis and Virus Cultured from Dromedary Camels in Saudi Arabia. MBio 5: e01146–14.

6. BarlanA, ZhaoJ, SarkarMK, LiK, McCrayPBJr, et al. (2014) Receptor variation and susceptibility to MERS coronavirus infection. J Virol 88 (9) 4953–61.

7. FalzaranoD, de WitE, RasmussenAL, FeldmannF, OkumuraA, et al. (2013) Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 19: 1313–1317.

8. ColemanCM, MatthewsKL, GoicocheaL, FriemanMB (2013) Wild type and innate immune deficient mice are not susceptible to the Middle East Respiratory Syndrome Coronavirus. J Gen Virol 95 (Pt 2) 408–12.

9. ScobeyT, YountBL, SimsAC, DonaldsonEF, AgnihothramSS, et al. (2013) Reverse genetics with a full-length infectious cDNA of the Middle East respiratory syndrome coronavirus. Proc Natl Acad Sci U S A 110: 16157–16162.

10. de WitE, PrescottJ, BaselerL, BushmakerT, ThomasT, et al. (2013) The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters. PLoS One 8: e69127.

11. RajVS, SmitsSL, ProvaciaLB, van den BrandJM, WiersmaL, et al. (2013) Adenosine Deaminase Acts as a Natural Antagonist for Dipeptidyl Peptidase 4 Mediated Entry of the Middle East Respiratory Syndrome Coronavirus. J Virol 88 (3) 1834–8.

12. ZhaoJ, LiK, Wohlford-LenaneC, AgnihothramSS, FettC, et al. (2014) Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A 111 (13) 4970–5.

13. MunsterVJ, de WitE, FeldmannH (2013) Pneumonia from Human Coronavirus in a Macaque Model. N Engl J Med 368 (16) 1560–2.

14. YaoY, BaoL, DengW, XuL, LiF, et al. (2013) An Animal Model of MERS Produced by Infection of Rhesus Macaques With MERS Coronavirus. J Infect Dis 209 (2) 236–42.

15. de WitE, RasmussenAL, FalzaranoD, BushmakerT, FeldmannF, et al. (2013) Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc Natl Acad Sci U S A 110: 16598–16603.

16. FalzaranoD, de WitE, MartellaroC, CallisonJ, MunsterVJ, et al. (2013) Inhibition of novel beta coronavirus replication by a combination of interferon-alpha2b and ribavirin. Sci Rep 3: 1686.

17. RajVS, MouH, SmitsSL, DekkersDH, MullerMA, et al. (2013) Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495: 251–254.

18. LuG, HuY, WangQ, QiJ, GaoF, et al. (2013) Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature 500: 227–231.

19. WangN, ShiX, JiangL, ZhangS, WangD, et al. (2013) Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res 23: 986–993.

20. van DoremalenN, MiazgowiczKL, Milne-PriceS, BushmakerT, RobertsonS, et al. (2014) Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through its Receptor Dipeptidyl Peptidase 4. J Virol pii: JVI.00676-14 [epub ahead of print].

21. ZakiAM, van BoheemenS, BestebroerTM, OsterhausAD, FouchierRA (2012) Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367: 1814–1820.

22. SchroederC, OsmanAA, RoggenbuckD, MothesT (1999) IgA-gliadin antibodies, IgA-containing circulating immune complexes, and IgA glomerular deposits in wasting marmoset syndrome. Nephrol Dial Transplant 14: 1875–1880.

23. PipesL, LiS, BozinoskiM, PalermoR, PengX, et al. (2013) The non-human primate reference transcriptome resource (NHPRTR) for comparative functional genomics. Nucleic Acids Res 41: D906–914.

24. LauSK, LauCC, ChanKH, LiCP, ChenH, et al. (2013) Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol 94: 2679–2690.

25. SiuKL, YeungML, KokKH, YuenKS, KewC, et al. (2014) Middle East respiratory syndrome coronavirus 4a protein is a double-stranded RNA-binding protein that suppresses PACT-induced activation of RIG-I and MDA5 in innate antiviral response. J Virol 88 (9) 4866–76.

26. YangX, ChenX, BianG, TuJ, XingY, et al. (2014) Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease. J Gen Virol 95: 614–626.

27. MatthewsKL, ColemanCM, van der MeerY, SnijderEJ, FriemanMB (2014) The ORF4b-encoded accessory proteins of MERS-Coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signaling. J Gen Virol 95 (Pt 4) 874–82.

28. YangY, ZhangL, GengH, DengY, HuangB, et al. (2013) The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein Cell 4: 951–961.

29. NiemeyerD, ZillingerT, MuthD, ZieleckiF, HorvathG, et al. (2013) Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist. J Virol 87: 12489–12495.

30. SeeleyEJ (2013) Updates in the management of acute lung injury: a focus on the overlap between AKI and ARDS. Adv Chronic Kidney Dis 20: 14–20.

31. GralinskiLE, BankheadA3rd, JengS, MenacheryVD, ProllS, et al. (2013) Mechanisms of severe acute respiratory syndrome coronavirus-induced acute lung injury. MBio 4: e00271–13.

32. PageC, GoicocheaL, MatthewsK, ZhangY, KloverP, et al. (2012) Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection. J Virol 86: 13334–13349.

33. RockxB, BaasT, ZornetzerGA, HaagmansB, SheahanT, et al. (2009) Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection. J Virol 83: 7062–7074.

34. Al-TawfiqJA, MomattinH, DibJ, MemishZA (2014) Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: an observational study. Int J Infect Dis 20: 42–6.

35. LarkinMA, BlackshieldsG, BrownNP, ChennaR, McGettiganPA, et al. (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23: 2947–2948.

36. PetreyD, XiangZ, TangCL, XieL, GimpelevM, et al. (2003) Using multiple structure alignments, fast model building, and energetic analysis in fold recognition and homology modeling. Proteins 53 Suppl 6: 430–435.

37. Ponder J (1999) TINKER-software tools for molecular design, version 3.7. Washington University: St. Louis, MO.

38. ZhouH, ZhouY (2002) Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction. Protein Sci 11: 2714–2726.

39. CormanVM, EckerleI, BleickerT, ZakiA, LandtO, et al. (2012) Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill 17: 20285.

40. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.

41. DobinA, DavisCA, SchlesingerF, DrenkowJ, ZaleskiC, et al. (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29: 15–21.

42. McCarthyDJ, ChenY, SmythGK (2012) Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation. Nucleic Acids Res 40: 4288–4297.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 8
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa