Numerous studies have documented the high frequency of blindness which accompanies the later stages of acquired immunodeficiency syndrome (AIDS). Two urgent issues concerning infection in patients with AIDS and in asymptomatic HIV-1 positive (HIV+) individuals as it related to corneal transplantation. Although HIV-1 has been isolated from the brain as well as ocular tissues and secretions, there is no data concerning the presence or absence of HIV-1 or HHV-6 in corneas from symptomatic or asymptomatic HIV+ individuals. The second issue is the etiology of AIDS-associated retinitis. Whether it is a response to infection with the AIDS virus itself, opportunistic herpes group viruses, or a result of mixed infection is currently unknown. Several opportunistic agents (herpes group virus) have been routinely associated with AIDS retinitis. Recently, a sixth human herpesvirus (HHV-6 or HBLV) has been isolated from 60-70% of AIDS patients and it has been postulated that it may be a key factor in activation of HIV-1 leading to development of the AIDS syndrome. Recently, using two different methods (histochemical and the polymerase chain reaction) we were able to demonstrate the presence of HIV-1 antigen and DNA sequences preliminary, this suggests a possible role of HHV-6 in AIDS retinitis. In the proposed study, corneas and retinas from AIDS patients and corneas from asymptomatic HIV+ individuals will be examined for the presence of HIV-1 and HHV-6 antigens (immunohistochemical method), homologous DNA sequence (in situ hybridization, polymerase chain reaction) and infectious potential (EM and virus cocultivation). Using technology generated, two mammalian cell lines will be isolated, one expressing the gag gene of HIV-1 and the other expressing a specific non-structural gene of HHV-6. These will provide a system for serological diagnosis of HIV-1 and HHV-6 and for screening potential antiviral agents for effectivity. Overall, this proposal will enhance our knowledge of AIDS-associated ocular diseases, with potential therapeutic improvements and definition of the risk of transmission of HIV-1 in corneal transplantation.
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