On the extinction probability in models of within-host infection: the role of latency and immunity
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Not every exposure to virus establishes infection in the host; instead, the small amount of initial virus could become extinct due to stochastic events. Different diseases and routes of transmission have a different average number of exposures required to establish an infection. Furthermore, the host immune response and antiviral treatment affect not only the time course of the viral load provided infection occurs, but can prevent infection altogether by increasing the extinction probability. We show that the extinction probability when there is a time-dependent immune response depends on the chosen form of the model—specifically, on the presence or absence of a delay between infection of a cell and production of virus, and the distribution of latent and infectious periods of an infected cell. We hypothesise that experimentally measuring the extinction probability when the virus is introduced at different stages of the immune response, alongside the viral load which is usually measured, will improve parameter estimates and determine the most suitable mathematical form of the model.
KeywordsMulti-type branching process Viral dynamics Within-host model Influenza Extinction probability Immune response
Mathematics Subject Classification92D30 60J70 60J80
The authors would like to thank Peter Taylor and Sophie Hautphenne for valuable discussions. Ada W. C. Yan is supported by an Australian Postgraduate Award. Pengxing Cao is supported by a National Health and Medical Research Council funded Centre for Research Excellence in Infectious Diseases Modelling to Inform Public Health Policy (1078068). James M. McCaw is supported by an Australian Research Council Future Fellowship (110100250).
- Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C (2012) Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 367(5):399–410CrossRefGoogle Scholar
- Bodewes R, Kreijtz JHCM, Geelhoed-Mieras MM, van Amerongen G, Verburgh RJ, van Trierum SE, Kuiken T, Fouchier RAM, Osterhaus ADME, Rimmelzwaan GF (2011) Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J Virol 85(6):2695–2702CrossRefGoogle Scholar
- Cao P, Yan AWC, Heffernan J, Petrie S, Moss RG, Carolan LA, Guarnaccia TA, Kelso A, Barr IG, McVernon J, Laurie KL, McCaw JM (2015) Innate immunity and the inter-exposure interval determine the dynamics of secondary influenza virus infection and explain observed viral hierarchies. PLOS Comput Biol 11(8):e1004,334CrossRefGoogle Scholar
- Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapía M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernández T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallás EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV (2010) Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 363(27):2587–2599CrossRefGoogle Scholar
- Jensen A (1948) An elucidation of A.K. Erlang’s statistical works through the theory of stochastic processes. Published in “The Erlangbook”: Brockmeyer E, Halstrøm HL, Jensen A: The life and works of AK Erlang København 1948, 23-100Google Scholar
- Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci 105(21):7552–7557CrossRefGoogle Scholar
- Keele BF, Li H, Learn GH, Hraber P, Giorgi EE, Grayson T, Sun C, Chen Y, Yeh WW, Letvin NL, Mascola JR, Nabel GJ, Haynes BF, Bhattacharya T, Perelson AS, Korber BT, Hahn BH, Shaw GM (2009) Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med 206(5):1117–1134CrossRefGoogle Scholar
- Laurie KL, Guarnaccia TA, Carolan LA, Yan AWC, Aban M, Petrie S, Cao P, Heffernan JM, McVernon J, Mosse J, Kelso A, McCaw JM, Barr IG (2015) The time-interval between infections and viral hierarchies are determinants of viral interference following influenza virus infection in a ferret model. J Infect Dis 212:1701–1710CrossRefGoogle Scholar
- Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, Henderson FL, Pathak SR, Soud FA, Chillag KL, Mutanhaurwa R, Chirwa LI, Kasonde M, Abebe D, Buliva E, Gvetadze RJ, Johnson S, Sukalac T, Thomas VT, Hart C, Johnson JA, Malotte CK, Hendrix CW, Brooks JT (2012) Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 367(5):423–434CrossRefGoogle Scholar