Influenza C and D Viruses Demonstrated a Differential Respiratory Tissue Tropism in a Comparative Pathogenesis Study in Guinea Pigs.

Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE

Publication: Washington Dc : American Society For Microbiology
Original Publication: Baltimore, American Society for Microbiology.

Guinea Pigs* ; Gammainfluenzavirus* ; Orthomyxoviridae Infections*/pathology ; Orthomyxoviridae Infections*/virology ; Thogotovirus* ; Disease Models, Animal*; Animals ; Humans ; Administration, Intranasal ; Receptors, Virus

Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal washes. The huICV replicated in the nasal turbinates, soft palate, and trachea but not in the lungs while swIDV replicated in all four tissues. A comparative analysis of tropism and pathogenesis of these two related seven-segmented influenza viruses revealed that swIDV-infected animals exhibited broad tissue tropism with an increased rate of shedding on 3, 5, and 7 dpi and high viral loads in the lungs compared to huICV. Seroconversion occurred late in the huICV group at 14 dpi, while swIDV-infected animals seroconverted at 7 dpi. Guinea pigs infected with huICV exhibited mild to moderate inflammatory changes in the epithelium of the soft palate and trachea, along with mucosal damage and multifocal alveolitis in the lungs. In summary, the replication kinetics and pathobiological characteristics of ICV in guinea pigs agree with the clinical manifestation of ICV infection in humans, and hence guinea pigs could be used to study these distantly related influenza viruses. IMPORTANCE Similar to influenza A and B, ICV infections are seen associated with bacterial and viral co-infections which complicates the assessment of its real clinical significance. Further, the antivirals against influenza A and B viruses are ineffective against ICV which mandates the need to study the pathobiological aspects of this virus. Here we demonstrated that the respiratory tract of guinea pigs possesses specific viral receptors for ICV. We also compared the replication kinetics and pathogenesis of huICV and swIDV, as these viruses share 50% sequence identity. The tissue tropism and pathology associated with huICV in guinea pigs are analogous to the mild respiratory disease caused by ICV in humans, thereby demonstrating the suitability of guinea pigs to study ICV. Our comparative analysis revealed that huICV and swIDV replicated differentially in the guinea pigs suggesting that the type-specific genetic differences can result in the disparity of the viral shedding and tissue tropism.
Competing Interests: The authors declare no conflict of interest.

J Gen Virol. 2021 Jan;102(1):. (PMID: 33211641)
Microbiol Immunol. 1986;30(5):451-60. (PMID: 3747863)
Euro Surveill. 2019 Mar;24(10):. (PMID: 30862333)
Viruses. 2019 Dec 27;12(1):. (PMID: 31892120)
Bioinformatics. 2015 Jan 15;31(2):166-9. (PMID: 25260700)
J Clin Virol. 2012 Jun;54(2):130-4. (PMID: 22398038)
mBio. 2014 Mar 04;5(2):e00031-14. (PMID: 24595369)
Emerg Infect Dis. 2019 Oct;25(10):1969-1972. (PMID: 31287050)
Transbound Emerg Dis. 2021 Nov;68(6):3396-3404. (PMID: 33259672)
PLoS Pathog. 2013 Feb;9(2):e1003176. (PMID: 23408893)
Virus Res. 1986 May;4(3):275-88. (PMID: 3739423)
PLoS One. 2012;7(12):e52249. (PMID: 23284954)
Emerg Infect Dis. 2020 Jan;26(1):173-176. (PMID: 31855544)
J Med Virol. 2014 May;86(5):879-85. (PMID: 24122799)
Science. 1987 Jun 5;236(4806):1293-5. (PMID: 3589663)
Clin Infect Dis. 2018 Mar 19;66(7):1092-1098. (PMID: 29069373)
J Vet Diagn Invest. 2020 Jul;32(4):585-588. (PMID: 32552516)
J Lab Clin Med. 1951 Nov;38(5):747-50. (PMID: 14889062)
J Clin Virol. 2016 Jan;74:50-3. (PMID: 26655269)
mSphere. 2017 Aug 9;2(4):. (PMID: 28808690)
J Infect Dis. 2001 Apr 15;183(8):1269-72. (PMID: 11262210)
J Virol. 2020 Jan 31;94(4):. (PMID: 31776281)
Arch Intern Med. 1980 Oct;140(10):1295-8. (PMID: 7425764)
Nature. 2015 Oct 1;526(7571):122-5. (PMID: 26416728)
J Clin Virol. 2016 Aug;81:31-3. (PMID: 27294672)
PLoS Pathog. 2016 Jan 27;12(1):e1005411. (PMID: 26816272)
Biol Chem Hoppe Seyler. 1987 May;368(5):451-4. (PMID: 3497642)
J Appl Physiol (1985). 1985 Feb;58(2):564-70. (PMID: 3980358)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Influenza Other Respir Viruses. 2016 Jan;10(1):27-33. (PMID: 26456848)
Virology. 1986 Aug;153(1):12-21. (PMID: 2943076)
Bull World Health Organ. 1953;8(5-6):613-31. (PMID: 13094497)
J Egypt Public Health Assoc. 1977;52(1):6-11. (PMID: 556274)
Acta Virol. 1983 Nov;27(6):502-10. (PMID: 6140836)
J Pediatr. 1991 Feb;118(2):235-8. (PMID: 1993950)
J Biol Chem. 1986 May 5;261(13):5947-51. (PMID: 3700379)
Vaccine. 1985 Sep;3(3 Suppl):182-8. (PMID: 4060845)
Emerg Infect Dis. 2018 Feb;24(2):389-391. (PMID: 29350168)
Vopr Virusol. 1984 Jul-Aug;29(4):420-3. (PMID: 6208688)
Am J Physiol Lung Cell Mol Physiol. 2005 Dec;289(6):L909-15. (PMID: 15937066)
Emerg Infect Dis. 2019 Jun;25(6):1224-1226. (PMID: 31107233)
Zoonoses Public Health. 2018 Feb;65(1):e148-e154. (PMID: 29139222)
Microbiol Resour Announc. 2018 Jul 12;7(1):. (PMID: 30533603)
J Virol. 2015 Dec;89(23):11990-2001. (PMID: 26378161)
Res Virol. 1992 May-Jun;143(3):199-204. (PMID: 1325663)
Emerg Infect Dis. 2017 Sep;23(9):1556-1559. (PMID: 28820371)
J Comp Pathol. 1984 Apr;94(2):273-83. (PMID: 6330181)
Kansenshogaku Zasshi. 1987 Feb;61(2):126-33. (PMID: 2440961)
Nucleic Acids Res. 2017 Jan 4;45(D1):D466-D474. (PMID: 27679478)
New Microbiol. 1993 Oct;16(4):367-71. (PMID: 8264427)
Am J Public Health Nations Health. 1949 Feb;39(2):171-8. (PMID: 18111593)
Emerg Infect Dis. 2018 Oct;24(10):1926-1929. (PMID: 30226175)
Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286)
J Virol. 2016 Aug 26;90(18):8251-65. (PMID: 27384661)
J Gen Virol. 1983 Jan;64 (Pt 1):177-82. (PMID: 6296296)
EMBO J. 1985 Jun;4(6):1503-6. (PMID: 2411539)
Am J Obstet Gynecol. 2004 Sep;191(3):847-55. (PMID: 15467552)
Transbound Emerg Dis. 2019 May;66(3):1379-1386. (PMID: 30873724)
Br Med J. 1957 Sep 14;2(5045):606-9. (PMID: 13460331)
Br Med J. 1968 Oct 19;4(5624):153-4. (PMID: 5681050)
Pediatr Infect Dis J. 2015 Nov;34(11):1273-5. (PMID: 26244834)
Virology. 1985 Oct 30;146(2):221-32. (PMID: 3855244)
J Endocrinol. 1971 Jun;50(2):329-37. (PMID: 5104492)
Infect Genet Evol. 2017 Oct;54:466-477. (PMID: 28803969)
Clin Infect Dis. 2019 Mar 5;68(6):972-975. (PMID: 30184114)
Trop Dis Travel Med Vaccines. 2020 Mar 12;6:5. (PMID: 32190346)
J Virol. 2018 May 14;92(11):. (PMID: 29514906)
Protein Cell. 2016 Jan;7(1):28-45. (PMID: 26215728)
Virus Res. 1997 Apr;48(1):71-9. (PMID: 9140195)
Diagn Microbiol Infect Dis. 2011 Apr;69(4):419-27. (PMID: 21396539)
Respiration. 2006;73(3):324-8. (PMID: 16195655)
Am J Epidemiol. 1968 Mar;87(2):440-6. (PMID: 5647870)
J Clin Microbiol. 2007 Mar;45(3):783-8. (PMID: 17215347)
Virology. 2020 Dec;551:10-15. (PMID: 33010670)
J Virol. 2019 Oct 15;93(21):. (PMID: 31413133)
Viruses. 2019 Feb 19;11(2):. (PMID: 30791465)
Microbiol Immunol. 1987;31(12):1173-80. (PMID: 2836710)
Emerg Infect Dis. 2019 Mar;25(3):607-609. (PMID: 30789339)
Microbiol Immunol. 1987;31(11):1137-43. (PMID: 3502168)
Bioinformatics. 2009 Aug 15;25(16):2078-9. (PMID: 19505943)
J Infect. 1992 Jan;24(1):91-9. (PMID: 1312564)
J Med Virol. 2016 Aug;88(8):1325-33. (PMID: 26773605)
J Gen Virol. 1991 Mar;72 ( Pt 3):711-4. (PMID: 1848603)
Eur J Epidemiol. 1994 Feb;10(1):91-4. (PMID: 7957798)
Jpn J Infect Dis. 2014;67(2):127-31. (PMID: 24647258)
Emerg Infect Dis. 2006 Oct;12(10):1621-2. (PMID: 17176596)
Infect Immun. 1980 Nov;30(2):500-5. (PMID: 7439993)
Vet Microbiol. 2015 Nov 18;180(3-4):281-285. (PMID: 26414999)
Zentralbl Bakteriol Orig A. 1975;231(1-3):47-56. (PMID: 1154916)
Vet Rec. 2014 Jan 25;174(4):96. (PMID: 24336761)
J Med Virol. 2022 Jun;94(6):2855-2859. (PMID: 34811769)
J Gen Virol. 1984 Nov;65 ( Pt 11):1873-80. (PMID: 6502139)
Tierarztl Prax. 1996 Aug;24(4):337-42. (PMID: 9012016)
J Clin Virol. 2019 Jun;115:47-52. (PMID: 30978620)

R01 AI141889 United States AI NIAID NIH HHS

Keywords: Guinea pigs; Influenza C; Influenza D; Tissue tropism; animal models; in vivo; influenza; pathogenesis; virulence

0 (Receptors, Virus)

Date Created: 20230518 Date Completed: 20230719 Latest Revision: 20240923

20240923

PMC10308911

10.1128/jvi.00356-23

37199648