PubMed · 9149657
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1997-05-01. CDC data on AIDS.. https://pubmed.ncbi.nlm.nih.gov/9149657/
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HIV-1 gene expression relies upon a complex machinery that is primarily controlled by two viral regulatory proteins, Tat and Rev. Rev is involved in regulating post-transcriptional events of HIV-1 gene expression. The Tat protein transactivates transcription from the HIV-1 5' long terminal repeat (LTR) and acts in synergy with specific cellular factors. Recently, it has been shown that one set of these cellular factors is a protein kinase activity termed TAK (Tat-associated kinase), which activates transcription by hyperphosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II. TAK also enhances transcription of HIV-2, together with the retroviral transactivator, Tat-2. The TAK activity appears to be related to the CTD kinase P-TEFb, which stabilizes transcription elongation of many genes and was originally isolated from Drosophila extracts. Both TAK and P-TEFb contain at least two subunits: the cyclin-dependent kinase, CDK9 (PITALRE), the catalytic subunit, and the regulatory subunit, cyclin T1. CDK9 and cyclin T1 are ubiquitous factors that affects many cellular processes, including cell differentiation and apoptosis. The involvement of TAK in HIV-1 and HIV-2 gene expression is an important aspect in the biology of these two retroviruses, and may lead to the development of novel antiretroviral drugs and/or gene therapy approaches for the treatment of patients with AIDS.
The spectrum of HIV-related lymphoid malignancies certainly includes non-Hodgkin's lymphoma (NHL; i.e., chiefly large-cell lymphoma and Burkitt's lymphoma), primary lymphoma of the brain (PBL) and, possibly, Hodgkin's disease (HD). Since the mid-1990s, several epidemiological studies have led to better quantification of the burden of lymphomas in HIV-infected populations. AIDS surveillance data from 17 western European countries show that between 1988 and 1997 a total of 7,148 AIDS cases had NHL as the AIDS-defining illness. The yearly number of cases rose steadily from 1988 to 1995 but declined thereafter. As a percentage of AIDS-defining illnesses, NHL increased from 3.6% in 1994 to 4.9% in 1997. Percent increases were observed in different strata by area, age group, sex and HIV-transmission group. To estimate relative risk (RR) of NHL and other lymphoid neoplasms in unselected HIV-seropositive populations, records of population-based cancer registries and AIDS registries were linked in the United States, Italy and Australia. RRs for NHL in adults with HIV/AIDS ranged between 14 (for low-grade NHL) to over 300 (for high-grade NHL). For HD, the RR was approximately 10. Limited findings from studies based on death certificates and cohorts of HIV-seropositive persons were consistent with those from registry linkage studies. In developing countries, the risk of HIV-associated NHL appears to be much lower than in developed countries, but under-ascertainment and earlier death from other AIDS manifestations may explain the lack of HIV-associated lymphomas in Africa.
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