Hughes, R; (2017) Herpesvirus and HIV-1 co-infection of human macrophages. Doctoral thesis , UCL (University College London).

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Abstract

HSV-1 and HIV-1 co-infection of human macrophages represents a clinically relevant model with which to investigate the host-pathogen interactions between macrophages and viruses. In this thesis, I demonstrate that HSV-1 productively infects human monocyte derived macrophages, with associated cell death and type I IFN responses, and additionally, that a proportion of macrophages support latent HSV-1 infection. I de ne latency as the absence of lytic gene transcription, virion production and cell death, in the presence of persistent expression of the HSV-1 latency associated transcript (LAT). I also demonstrate that HSV-1 super-infection increases HIV-1 transcription, and that latent HSV-1 can be reactivated by HIV-1. HSV-1 latent infection of neurons is well established, but this is the rst report, to my knowledge, of HSV-1 latent infection of myeloid lineage cells. The potential for macrophage reservoirs of latent HSV-1 may be an important factor for the clinical management of persistent reactive HSV-1 disease. Furthermore, HIV-1 infection in vivo is known to increase the frequency of HSV-1 reactivation in the host through the indirect mechanism of immune system suppression. However, a direct interaction between cells latently infected with HSV and HIV-1 has not previously been observed. Reactivation of latent HSV by HIV-1 therefore provides a novel mechanism for the well-established clinical synergy between these viruses.

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