Summary:
HIV-1 entry to the CNS is facilitated by loss of the integrity of the blood brain barrier early in HIV infection. Poor drug penetration and reduced immune surveillance contributes to establishment of a reservoir. This presents four problems. 1) It is implicated in the aetiology of HIV encephalitis and HIV associated brain injury (HABI) 2) it may lead to viral rebound if treatment is stopped 3) it is implicated in neurodevelopmental problems in utero and 4) it is a barrier to achieving HIV cure. HIV variants co-exist in anatomical distinct compartments, the brain being one such compartment.
You will utilise bio-banked specimens from clinical studies in people living with HIV to characterise the genetic and phenotypic properties of HIV independently replicating in the CNS. You will clone patient derived HIV genomes into vector and generate pseudotyped viruses which will be used in downstream experiments to study co-receptor usage by infection of U87 cells expressing either CCR5 or CXCR4 co-receptors; cellular tropism by infection of monocyte derived macrophages (MDMs) and microglia; R5 co-receptor affinity by infection of Affinophile cells with inducible levels of CD4 and CCR5; and neurovirulence in iPSC-derived microglia/neuron co-cultures.
Desirable knowledge or skills:
An interest in virology, cell culture experience, able to understand own limitations and ask questions if unsure and overall a passion for science and acquiring new knowledge. Hepatitis B immunity is also required due to lab work safety (please get in touch with the supervisor for related questions).
Supervisor:
Dami Collier, Department of Pathology, University of Cambridge (adc82@cam.ac.uk)