Human immunodeficiency virus-1 (HIV-1) gene expression is controlled by cellular transcription factors and by virally encoded trans-activation proteins of the HIV-1 tat and art/trs genes, which are essential for viral replication. Tat trans-activates HIV-1 gene expression by interacting with the trans-acting response element (TAR) located within the HIV-1 long terminal repeat (LTR) (ref. 2). In transient expression assays, tat mediates its effects largely by increasing the steady-state levels of messenger RNA species that contain the TAR sequence at or near their 5' ends, suggesting a function for tat either in transcription or in subsequent RNA processing. The tat gene could also facilitate translation of mRNA containing the TAR sequence. To determine the mechanism of trans-activation by tat, we analysed the structure and rate of synthesis of RNA species directed by the HIV-1 LTR in transient expression assays both in the presence and absence of tat. Although the rate of HIV-1 transcription initiation was not affected by tat, transcriptional elongation beyond position +59 was seen only in the presence of tat. Thus, tat trans-activates HIV-1 transcription by relieving a specific block to transcriptional elongation within the TAR sequence.

Antibody-mediated poliovirus neutralization was studied by using a series of 13 monospecific neutralizing antibodies. These antibodies were found to recognize seven individual viral epitopes, several of which functionally overlap one another. Each epitope was capable of undergoing variation so that the variant virus was no longer capable of being neutralized by antibody directed against that epitope. The measured degree of variation for each site varied from-3.1 to-4.2 log1o variant PFU per wild-type PFU. Under nonsaturating but neutralizing conditions, the antibodies, with the exception of those directed to one specific epitope, failed to completely inhibit the virion's binding to the cell. Similarly, none of the neutralizing antibodies completely inhibited viral penetration, but all prevented virus-specific transcription. A strong correlation was established between the binding of each of the neutralizing antibodies, with one exception, to the virion and a significant shift in the virion's pl from 7.0 to ca. 4.0.

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