Don Ganem Part 3 KSHV Latency and KS Pathogenesis
In 1872, Moritz Kaposi first described a disease that included pigmented skin tumors and in some cases tumors of the viscera. While KS has been endemic in some areas of the world for many years, a highly aggressive and deadly form of the disease emerged concurrently with the HIV/AIDS epidemic. KS is a very unusual cancer including multiple cell types, including cells of a spindle morphology, in a single tumor. In this section of the talk, the atypical biology of this cancer it will be discussed. Epidemiological studies suggested that HIV was not the causative agent of KS. In the mid-1990s, a new human herpes virus, Kaposis sarcoma associated herpes virus (KSHV), was identified as the likely cause of KS. Development of a serological test for the presence of KSHV in patients showed that KS seroprevalence strikingly mirrored KS risk and, additionally, KS was never found in KSHV negative patients. This data strongly supported KSHV as the causative agent of KS. However, epidemiology also showed that additional cofactors are required for disease development and in the case of patients with AIDS, HIV is this cofactor. In this section of the lecture, we will look at which viral genes are expressed in KS and how they cause disease. KSHV has both a latent and lytic cycle. In the latency cycle, very few genes are expressed and no new virus is produced allowing the host cell to survive. In the lytic cycle, all open reading frames are expressed, new virus produced and the host cell ...
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