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A human immunodeficiency virus type 1 (HIV-1) derivative (HIVNL-DT5R) containing sequences encoding a 7-amino-acid segment of CA and the entire vif gene from simian immunodeficiency virus (SIV) was previously shown to establish spreading infections in cultured macaque peripheral blood mononuclear cells. To assess its replicative and disease-inducing properties in vivo, HIVNL-DT5R was inoculated into pig-tailed macaques. HIVNL-DT5R generated plasma viremia in all five of the monkeys and elicited humoral responses against all of the HIV-1 structural proteins but did not cause CD4+ T-lymphocyte depletion or clinical disease. Additional adaptation will be required to optimize infectivity in vivo.

Monkey infection models are absolutely necessary for studies of human immunodeficiency virus type 1 (HIV-1) pathogenesis and of developing drugs/vaccines against HIV-1. In addition, currently unknown roles of its accessory proteins for in vivo replication await elucidation by experimental approaches. Due to the fact that HIV-1 is tropic only for chimpanzees and humans, studies of this line have been impeded for a long time, although various investigations have been carried out utilising genetically related SIV and SIV/HIV chimeric virus (SHIV) as pathogens. Recent findings of anti-HIV-1 innate factors such as tripartite motif protein 5alpha (TRIM5alpha) and APOBEC3G/F prompted us to re-initiate an old and vital research project which would, as a result, confer the capability to overcome the species barrier on the HIV-1. We currently have obtained, by virus engineering through genetic manipulation and adaptation, some new and promising HIV-1 clones for in vivo studies in macaque monkeys as mentioned above. In this review, we summarise the past, present and future of HIV-1/SIV chimeric viruses with special reference to relevant basic HIV-1/SIV studies.

Since the discovery of TT virus (TTV) in 1997, its mechanism of transcriptional control has remained unsolved. Molecular analysis points at the 1.2-kb noncoding region (NCR) as being responsible for transcriptional control. The 5' terminus of TTV mRNA was located at nt 114 using the primer extension method (nt 114 will be referred to as position +1). This employed the PE1 primer, designed to start approximately 100 nt downstream of the predicted initiation site. Overall promoter and enhancer activity of the NCR was analyzed using dual luciferase assays in K562, Jurkat, U937, A549, HepG2, Huh7, and HeLaS3 cells. Of those tested, K562 showed the highest relative luciferase activity of 31.1, and activity in HepG2 (14.6) was significantly higher than that in Huh7 (2.8). Fragments of <250 nt length, spanning the NCR, were inserted into a luciferase vector possessing an SV40 promoter. Fragments F5(-542/-311) and F6(-310/-197) showed promoter-enhancing activities of >6.0 by insertion not only in the sense orientation, but also both in the antisense orientation and downstream of the luciferase gene. The 5' deletion of NCR from -1201 to -370 resulted in no significant decrease in the level of luciferase activity. A gradual decrease in the activity of the 5'-deletion mutants from position -370 through -155 was consistent with the loss of enhancer binding sites detected during fragment analysis. A further deletion at position -76 completely abolished luciferase expression, indicating that region -154/-76 contains the critical regulatory element for functioning of the TTV promoter.