Influenza A Virus Transmission Bottlenecks Are Defined by Infection Route and Recipient Host

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2014 Dec 3

PMID 25456074

Citations 139

Authors

Andrew Varble

Randy A Albrecht

Simone Backes

Marshall Crumiller

Nicole M Bouvier

David Sachs

Adolfo Garcia-Sastre

Benjamin R tenOever

Affiliations

Soon will be listed here.

Abstract

Despite its global relevance, our understanding of how influenza A virus transmission impacts the overall population dynamics of this RNA virus remains incomplete. To define this dynamic, we inserted neutral barcodes into the influenza A virus genome to generate a population of viruses that can be individually tracked during transmission events. We find that physiological bottlenecks differ dramatically based on the infection route and level of adaptation required for efficient replication. Strong genetic pressures are responsible for bottlenecks during adaptation across different host species, whereas transmission between susceptible hosts results in bottlenecks that are not genetically driven and occur at the level of the recipient. Additionally, the infection route significantly influences the bottleneck stringency, with aerosol transmission imposing greater selection than direct contact. These transmission constraints have implications in understanding the global migration of virus populations and provide a clearer perspective on the emergence of pandemic strains.

Citing Articles

Animal Models in Influenza Research.

Zhou J, Hemmink J, Whittaker C, Shelton H, Peacock T Methods Mol Biol. 2025; 2890:53-88.

PMID: 39890721 DOI: 10.1007/978-1-0716-4326-6_3.

Dispersal of influenza virus populations within the respiratory tract shapes their evolutionary potential.

Ferreri L, Seibert B, Caceres C, Patatanian K, Holmes K, Gay L Proc Natl Acad Sci U S A. 2025; 122(4):e2419985122.

PMID: 39835898 PMC: 11789087. DOI: 10.1073/pnas.2419985122.

Barcoded SARS-CoV-2 viruses define the impact of duration and route of exposure on the transmission bottleneck in a hamster model.

Trende R, Darling T, Gan T, Wang D, Boon A Sci Adv. 2025; 11(3):eads2927.

PMID: 39813353 PMC: 11778309. DOI: 10.1126/sciadv.ads2927.

Unraveling the genomic landscape of piscine myocarditis virus: mutation frequencies, viral diversity and evolutionary dynamics in Atlantic salmon.

Amono R, Markussen T, Singh V, Lund M, Manji F, Mor S Virus Evol. 2024; 10(1):veae097.

PMID: 39717704 PMC: 11665822. DOI: 10.1093/ve/veae097.

Quantifying the impact of vaccination on transmission and diversity of influenza A variants in pigs.

Li C, Culhane M, Schroeder D, Cheeran M, Galina Pantoja L, Jansen M J Virol. 2024; 98(12):e0124524.

PMID: 39530665 PMC: 11651001. DOI: 10.1128/jvi.01245-24.

References

Maines T, Jayaraman A, Belser J, Wadford D, Pappas C, Zeng H . Transmission and pathogenesis of swine-origin 2009 A(H1N1) influenza viruses in ferrets and mice. Science. 2009; 325(5939):484-7. PMC: 2953552. DOI: 10.1126/science.1177238. View

Smith G, Vijaykrishna D, Bahl J, Lycett S, Worobey M, Pybus O . Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature. 2009; 459(7250):1122-5. DOI: 10.1038/nature08182. View

White L, Wallinga J, Finelli L, Reed C, Riley S, Lipsitch M . Estimation of the reproductive number and the serial interval in early phase of the 2009 influenza A/H1N1 pandemic in the USA. Influenza Other Respir Viruses. 2009; 3(6):267-76. PMC: 2782458. DOI: 10.1111/j.1750-2659.2009.00106.x. View

van Riel D, den Bakker M, Leijten L, Chutinimitkul S, Munster V, de Wit E . Seasonal and pandemic human influenza viruses attach better to human upper respiratory tract epithelium than avian influenza viruses. Am J Pathol. 2010; 176(4):1614-8. PMC: 2843453. DOI: 10.2353/ajpath.2010.090949. View

Wang G, Sherrill-Mix S, Chang K, Quince C, Bushman F . Hepatitis C virus transmission bottlenecks analyzed by deep sequencing. J Virol. 2010; 84(12):6218-28. PMC: 2876626. DOI: 10.1128/JVI.02271-09. View

Varble A, Chua M, Perez J, Manicassamy B, Garcia-Sastre A, tenOever B . Engineered RNA viral synthesis of microRNAs. Proc Natl Acad Sci U S A. 2010; 107(25):11519-24. PMC: 2895125. DOI: 10.1073/pnas.1003115107. View

Seibert C, Kaminski M, Philipp J, Rubbenstroth D, Albrecht R, Schwalm F . Oseltamivir-resistant variants of the 2009 pandemic H1N1 influenza A virus are not attenuated in the guinea pig and ferret transmission models. J Virol. 2010; 84(21):11219-26. PMC: 2953187. DOI: 10.1128/JVI.01424-10. View

Lauring A, Andino R . Exploring the fitness landscape of an RNA virus by using a universal barcode microarray. J Virol. 2011; 85(8):3780-91. PMC: 3126141. DOI: 10.1128/JVI.02217-10. View

Gustin K, Belser J, Wadford D, Pearce M, Katz J, Tumpey T . Influenza virus aerosol exposure and analytical system for ferrets. Proc Natl Acad Sci U S A. 2011; 108(20):8432-7. PMC: 3100970. DOI: 10.1073/pnas.1100768108. View

10.

Chou Y, Albrecht R, Pica N, Lowen A, Richt J, Garcia-Sastre A . The M segment of the 2009 new pandemic H1N1 influenza virus is critical for its high transmission efficiency in the guinea pig model. J Virol. 2011; 85(21):11235-41. PMC: 3194962. DOI: 10.1128/JVI.05794-11. View

11.

Imai M, Watanabe T, Hatta M, Das S, Ozawa M, Shinya K . Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012; 486(7403):420-8. PMC: 3388103. DOI: 10.1038/nature10831. View

12.

Herfst S, Schrauwen E, Linster M, Chutinimitkul S, de Wit E, Munster V . Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012; 336(6088):1534-41. PMC: 4810786. DOI: 10.1126/science.1213362. View

13.

Russell C, Fonville J, Brown A, Burke D, Smith D, James S . The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science. 2012; 336(6088):1541-7. PMC: 3426314. DOI: 10.1126/science.1222526. View

14.

Forrester N, Guerbois M, Seymour R, Spratt H, Weaver S . Vector-borne transmission imposes a severe bottleneck on an RNA virus population. PLoS Pathog. 2012; 8(9):e1002897. PMC: 3441635. DOI: 10.1371/journal.ppat.1002897. View

15.

Chua M, Schmid S, Perez J, Langlois R, tenOever B . Influenza A virus utilizes suboptimal splicing to coordinate the timing of infection. Cell Rep. 2013; 3(1):23-9. PMC: 3563938. DOI: 10.1016/j.celrep.2012.12.010. View

16.

Milton D, Fabian M, Cowling B, Grantham M, McDevitt J . Influenza virus aerosols in human exhaled breath: particle size, culturability, and effect of surgical masks. PLoS Pathog. 2013; 9(3):e1003205. PMC: 3591312. DOI: 10.1371/journal.ppat.1003205. View

17.

Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W . Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013; 368(20):1888-97. DOI: 10.1056/NEJMoa1304459. View

18.

Cowling B, Ip D, Fang V, Suntarattiwong P, Olsen S, Levy J . Aerosol transmission is an important mode of influenza A virus spread. Nat Commun. 2013; 4:1935. PMC: 3682679. DOI: 10.1038/ncomms2922. View

19.

Baker S, Guo H, Albrecht R, Garcia-Sastre A, Topham D, Martinez-Sobrido L . Protection against lethal influenza with a viral mimic. J Virol. 2013; 87(15):8591-605. PMC: 3719819. DOI: 10.1128/JVI.01081-13. View

20.

Dorigatti I, Cauchemez S, Ferguson N . Increased transmissibility explains the third wave of infection by the 2009 H1N1 pandemic virus in England. Proc Natl Acad Sci U S A. 2013; 110(33):13422-7. PMC: 3746905. DOI: 10.1073/pnas.1303117110. View