HIV-1 adaptation to the host: The viral capsid and host factors

The Human Immunodeficiency Virus (HIV-1) depends on interaction with many host factors for a successful replication and infection, however some interacting host factors are part of the host defense against invading viruses and are detrimental for the virus. Due to immune pressure, high viral turnover and error-prone nature of HIV-1, changes in the dynamics of those interactions may occur and have consequences on biological properties of the virus and course of infection. In this thesis we studied the interaction of the HIV-1 capsid with host factors and how changes in the virus affect these interactions, viral infectivity and disease progression.
Here we studied the effect of mutations in viral capsid in the CypA-binding region on the biological properties of the virus. Furthermore, we analyzed whether HIV-1 was able to adapt to replicate in the presence of rhTrim5α, and determined whether escape mutations only emerged in capsid or whether the virus could escape rhTrim5α-mediated restriction by introduction of amino acid changes in other viral proteins. Moreover, we studied the dynamics of mutations in HLA-B*27 restricted epitopes in the viral capsid in HIV-1 infected patients carrying this protective HLA-B*27 allele, and analyzed whether viral escape was associated with disease progression. Additionally, the effect of genetic polymorphisms in host factor TREX1 were analyzed with regard to HIV-1 pathogenesis in the Amsterdam Cohort Studies on HIV-1 and AIDS. Finally, these described findings are discussed in the light of current view how the HIV-1 interaction with host factors is relevant in HIV-1 infection and immune evasion.