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Previous research has focused on understanding genotypic and phenotypic differences in the HIV-1 gp120 molecule and how these influence HIV-1 infection and disease progression. We have established that two HV-1 subtype C strains (C & C’) co-circulate in Ethiopia and demonstrated that these strains spread differently are causing altered disease progression profiles. We have also studied the biological properties of subtype C viruses and shown that they vary considerably from the other subtypes, especially in their lack of capacity to switch in co-receptor usage from CCR5 to CXCR4 using. We have also studied in depth the molecular changes that occur in the envelope to facilitate this switch in co-receptor usage. The group has also been involved in the development of new molecular assays to detect HIV-1 infection. These assays have also been used to detect HIV-1 in sera and human milk in clinical samples from Ethiopia. Assays have also been developed to allow for the quantification of specific viral life-cycle stages in cells, i.e. determination of intracellular viral loads. We have shown with this assay that an array of cell types from the innate arm of the immune response can be infected with HIV-1 to high levels.
To date the main research focus has become the characterization of the molecular characteristics of the gp120 protein with regards to transmission and disease progression. Better defining which host factors can influence which virus genotypes/phenotypes undergo transmission or propagation will undoubtedly aide in future development of HIV-1 vaccines and/or microbicides.
In close collaboration with the clinic we have been recruiting individuals identified during primary HIV-1 infection period and collecting blood. When possible we also obtain material from the donor case. From this material we can cell sort different cell types of both the innate and adaptive arms of the immune system and assay for HIV-1 infection levels. We have additionally established a number of phenotypic assays that can enable us to amplify envelope from these different cellular fractions and assay for variant phenotypes. This analysis in combination with the genotypic analysis will enable for us to match the variant envelope phenotypes with biological function. From the same materials we also aim to utilize the new power sequencing tools to identify which viral variants are present which each of the particular cell types. Materials will be collected from these individuals longitudinally which will enable us to monitor what consequences the induced immune responses have on
Over the years we have established other cohorts where we propose to study the same as outlined above. We have a number of scenarios where we have identified clusters of HIV-1 infection, where a group of individuals have been infected with genetically linked HIV-1 variants and where we have materials from the donor and recipient cases over time. This covers both sexual transmission as well as vertical transmission of HIV-1. In addition, from a mother to child transmission cohort in Rwanda we have access to mother to child transmission cases of subtype A and C HIV-1. From this we propose to study which gp120 envelope characteristics can be associated which this route of transmission