HIV; HCV; virus dynamics; CD8+ T cell response; immune escape; T-cell-based vaccine; mathematical modeling
Althaus Christian Lorenz (2015), Ebola superspreading, in The Lancet Infectious Diseases
, 15(5), 507-508.
Althaus C.L., Low N., Musa E.O., Shuaib F., Gsteiger S. (2015), Ebola virus disease outbreak in Nigeria: Transmission dynamics and rapid control, in Epidemics
, 11(0), 80-84.
Althaus Christian Lorenz (2015), Of mice, macaques and men: scaling of virus dynamics and immune responses, in Frontiers in Microbiology
, 6(355), 1-3.
Kucharski A J, Althaus C L (2015), The role of superspreading in Middle East respiratory syndrome coronavirus (MERS-CoV) transmission., in Euro surveillance : bulletin Européen sur les maladies transmissibles = European communicable diseas
, 20(25), 14-18.
Althaus Christian L, Turner Katherine M E, Mercer Catherine H, Auguste Peter, Roberts Tracy E, Bell Gill, Herzog Sereina A, Cassell Jackie A, Edmunds W John, White Peter J, Ward Helen, Low Nicola (2014), Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling., in Health technology assessment (Winchester, England)
, 18(2), 1-100.
Althaus Christian L, Joos Beda, Perelson Alan S, Günthard Huldrych F (2014), Quantifying the turnover of transcriptional subclasses of HIV-1-infected cells., in PLoS computational biology
, 10(10), 1003871-1003871.
Low Nicola, Heijne Janneke Cornelia Maria, Herzog Sereina Annik, Althaus Christian Lorenz (2014), Reinfection by untreated partners of people treated for Chlamydia trachomatis and Neisseria gonorrhoeae: mathematical modelling study., in Sexually transmitted infections
Heijne Janneke C M, Herzog Sereina A, Althaus Christian L, Low Nicola, Kretzschmar Mirjam (2013), Case and partnership reproduction numbers for a curable sexually transmitted infection., in Journal of theoretical biology
, 331, 38-47.
Herzog Sereina A, Heijne Janneke C M, Scott Pippa, Althaus Christian L, Low Nicola (2013), Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study., in Epidemiology (Cambridge, Mass.)
, 24(6), 854-62.
Heijne Janneke Cornelia Maria, Herzog Sereina Annik, Althaus Christian Lorenz, Tao Guoyu, Kent Charlotte Kathleen, Low Nicola (2013), Insights into the timing of repeated testing after treatment for Chlamydia trachomatis: data and modelling study., in Sexually transmitted infections
, 89(1), 57-62.
Althaus Christian, Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa, in PLOS Currents: Outbreaks
Althaus Christian L., Salathé Marcel, Measles Vaccination Coverage and Cases among Vaccinated Persons, in Emerg Infect Dis
Background:Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are potentially fatal RNA virus infections of public health importance. Both viruses can cause chronic persistence in infected individuals. Some patients, however, can clear HCV spontaneously during the acute phase of infection. For HIV, some individuals have been shown to control virus replication very effectively which results in a delayed disease progression. One key factor that has been found to determine the outcome of an infection is an individuals CD8+ T cell response which can suppress viral replication or mediate cytotoxic killing of infected cells. Due to their high mutation rate, both HIV and HCV can evade these immune responses through the occurrence of immune escape, i.e., mutant viral variants with altered epitopes that are not recognized by CD8+ T cells anymore. Together, there is a large body of evidence showing that CD8+ T cells induce a selection pressure on HIV and HCV. Mathematical modeling of virus dynamics has provided important insights into the interplay between viral replication and the immune response of the host. Nevertheless, it remains unclear when, how and to what extent the CD8+ T cells do interfere with HIV or HCV replication.Aims:The aims of this research project are: 1) to decipher characteristic aspects of the viral dynamics and evolution of HIV and HCV during the acute and chronic phase; 2) to use these insights in order to model the virus dynamics of HIV and HCV, specifically addressing the potential role of the CD8+ T cell response during the acute and chronic phase of both infections; 3) to investigate the epidemiological consequences of the observed within-host dynamics and evolution of HIV in response to the CD8+ T cell selection pressure with mathematical and computational models.Methods:Mathematical modeling of virus dynamics is a truly interdisciplinary research field and it is crucial to establish close collaborations with clinical experts and epidemiologists. To this end, I will use patient data provided from different institutions: the University Clinic of Infectious Diseases (University of Bern), the Division of Infectious Diseases and Hospital Epidemiology (University Hospital Zurich), the Swiss HIV Cohort Study (SHCS) and the Murdoch University in Perth (Australia).For the first aim of the project, I will analyze four different data sets from these institutions in order to study characteristic aspects of HIV and HCV during the acute and chronic phase of infection. Specifically for HIV, I will investigate the decay dynamics of the virus after combination antiretroviral therapy (cART) which provides information on the overall viral turnover and the lifespan of HIV-infected cells. For HCV, I will study the viral dynamics and evolution, in particular the occurrence of immune escape, which can provide information on the selection pressure that is induced on the virus population through the CD8+ T cell response.The insights from the data analysis are being used in the second aim of the project, where I will develop virus dynamics models based on ordinary differential equations that take into account the characteristic aspects of the viral dynamics and evolution of HIV and HCV. This will help to conceptually study the potential role that CD8+ T cells can play during the acute and chronic phase of an infection.For the third aim of the project, I will study the processes of viral adaptation within a host and between hosts with respect to immune escape in HIV by using mathematical and computational models. This will allow to critically investigate the interplay between the within-host evolution, the transmission of the virus and the immune system diversity of the host population.Rationale and significance:This research project will provide novel insights into the dynamics of HIV and HCV during the acute and chronic phase of infection. A better understanding of the characteristic properties of both viruses will help to better explain the outcome of an infection, e.g., why natural clearance only occurs in HCV but not in HIV and whether CD8+ T cells play a pivotal role in this process. Lastly, the novel insights into the population level adaption of HIV in respect to immune evasion from CD8+ T cell responses are of great interest to anticipate the ongoing epidemics, in particular in light of current efforts for vaccine design.