Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Analysis of three distinct stages of replication in human retroviruses.
Diss Abstr Int [B]; 53(12):6113 1993. Unique Identifier : AIDSLINE ICDB/94696141 Hammes SR; Duke Univ.
Abstract:
The type 1 human immunodeficiency and human T-cell leukemia viruses (HIV-1 and HTLV-I, respectively) use many mechanisms at various stages throughout their life cycles to regulate replication. Three of these processes were examined in detail in order to better understand some of the complexities of this regulation. The first mechanism studied involved the regulation of retroviral gene transcription. HIV-1 Nef protein has been reported to control viral replication by suppressing gene transcription directed by the HIV-1 LTR. In contrast, these studies demonstrate that Nef had no effect on transcriptional activity through the HIV-1 LTR. Furthermore, HIV-1 proviral clones containing either a wild type or mutated nef gene replicated equally well when transfected into cells. These findings suggest that, in contrast to previous reports, Nef is neither a transcriptional inhibitor nor a suppressor of viral replication. The second regulatory mechanism examined was the control of retroviral structural protein expression. HTLV-I Rex protein acts post-transcriptionally to enhance expression of incompletely spliced viral mRNAs encoding these structural proteins. Rex function involves its direct interaction with an RNA stem-loop structure located within the 3' LTR termed the Rex response element (RexRE). This interaction requires a positively charged arginine-rich domain in Rex that also serves as a nuclear localization signal. Mutagenesis of this basic region revealed that, while positive charge alone appears sufficient for nuclear localization, multiple arginine residues at specific sites are essential for complete RNA binding and functional activity of Rex. The final stage of retroviral replication studied was viral binding to target cells. Little is known about the identity of the HTLV-I receptor. These studies demonstrated that a direct interaction between the HTLV-I envelope glycoprotein gp46 and viral receptors on target cells was necessary for infection. Binding assays using purified gp46 revealed that HTLV-I receptors were expressed on all mammalian tumor lines tested, but were absent on non-mammalian cells. Furthermore, activation of resting primary human T-lymphocytes, which are devoid of gp46 binding sites, resulted in the induction of HTLV-I receptor expression. Together, these results suggest that HTLV-I infection may require T-cell activation, and that HTLV-I receptor expression may correlate with cellular proliferation. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD93-11846)
Keywords: Gene Products, nef/*GENETICS Genes, pX/*GENETICS HIV Long Terminal Repeat/GENETICS HTLV-I/*GENETICS/PHYSIOLOGY HTLV-I Infections/GENETICS Lymphocyte Transformation Receptors, HIV/METABOLISM RNA Splicing T-Lymphocytes/PHYSIOLOGY Transcription, Genetic *Virus Replication THESIS
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
