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At least 1,603 records · Page 89Linked to original sources
PubMed1994

Basal and Tat-transactivated expression from the human immunodeficiency virus type 1 long terminal repeat in human placental trophoblast rules out promoter-enhancer activation as the partial block to viral replication.

We have analysed the capacity of the trophoblast-derived malignant cell lines BeWo, JAR and JEG-3, and primary cultures of highly purified trophoblast cells to support the basal and Tat-mediated trans-activation-enhanced transcriptional activity of two distinct human immunodeficiency virus type 1 (HIV-1) isolates. Kinetic studies based on expression of long terminal repeat (LTR)-chloramphenicol acetyltransferase (CAT) constructs revealed that LTRs of both the prototype strain 3B and the highly cytopathic Zairean variant NDK were activated significantly in all target cells. Overall, the strongest activation was observed in primary trophoblasts. A novel modification of quantitative PCR was used to normalize LTR expression for transfection efficiency, enabling the calculation of specific expression rates in terms of muU CAT enzyme per fmol of transfected DNA. Using the latter criterion we determined that LTRs of both viruses were activated in decreasing order from trophoblasts to JAR, JEG-3 and BeWo cells; furthermore, the expression of HIV-1 3B LTR always significantly surpassed that of HIV-1 NDK. The effects of trans-activation on either of the LTRs, when assayed in cotransfection assays with various amounts of HIV-1 NDK-Tat expression vector, increased in a dose-dependent fashion and were comparable in a particular neoplastic cell line. Furthermore, the cell-specific LTR activity patterns did not correspond to the abundance of transcription factors binding specifically to the viral NF kappa B and SP1 motifs. Unlike SP1-binding proteins which were relatively abundant, substantially smaller amounts of proteins with NF kappa B specificity were found in all cells. Despite this apparent deficit in NF kappa B activity, trophoblasts supported a high basal activity of both LTRs. These data indicate that an insufficiency of basal or Tat-trans-activated LTR activity cannot account for the low level of HIV-1 replication in this important cell type.

Base Sequence↗
PubMed1999

Histological localization of acetyltransferases in human tissue.

The localization of human arylamine acetyltransferases (NAT) transcripts was performed by non-isotopic in situ hybridization, utilizing a combination of six NAT1 or NAT2 specific antisense oligonucleotide probes, in order to identify those tissues and organs that might be susceptible to the carcinogenic effects of aromatic amines. The intratissue differences in the level of NAT mRNA were observed: the most abundant NAT2 transcripts were found in hepatocytes, while NAT1 ones dominated in the urothelium and in the colon epithelial cells. The specific NAT1 and NAT2 mRNAs were present also in the epithelial lining of the lung bronchi, the mammary gland and the small intestine epithelial cells, the outer layer of placenta syncytiotrophoblast cells, the kidney tubules, and the pineal gland. Qualitative differences in the sites of mRNA of these two enzymes were seen only in the kidney specimens, in which NAT2 was expressed in both proximal and distal tubules, and the NAT1 was detected only in the former ones.

Acetyltransferases↗
PubMed1999

Both phyA and phyB mediate light-imposed repression of PHYA gene expression in Arabidopsis.

The negatively photoregulated PHYA gene has a complex promoter structure in Arabidopsis, with three active transcription start sites. To identify the photoreceptors responsible for regulation of this gene, and to assess the relative roles of the three transcription start sites, we analyzed the changes in PHYA transcript levels in wild-type and photoreceptor mutant seedlings under various irradiation conditions. Continuous far-red or red light exposures each induced a significant decline in transcript levels in wild-type etiolated seedlings. Analysis of mutants specifically lacking either phyA or phyB protein demonstrated that these phytochromes are required for the negative regulation induced by far-red and red light, respectively. Ribonuclease protection experiments showed further that this negative regulation is confined almost exclusively to the shortest, most abundant PHYA transcript, and occurs predominantly in shoots. By contrast, both of the other minor transcripts in shoots, and all three transcripts in roots, exhibit near constitutive expression. This complex expression pattern indicates that the PHYA gene is subject to regulation by multiple signals, including environmental, developmental, and organ-specific signals.

Arabidopsis↗
PubMed1990

Alternatively spliced transcripts of the sex-determining gene tra-2 of Drosophila encode functional proteins of different size.

The Drosophila transformer-2 gene (tra-2) is required for female sex determination in somatic cells and for spermatogenesis in male germ cells. We studied the organization of the tra-2 gene and characterized the transcripts in wild type and mutant animals. Two transcripts are detected in males and females; they differ in their abundance and in the presence (minor transcript Tmin) or absence (major transcript Tmaj) of one exon. Two other transcripts are present only in male germ cells. One of these is rare (msTmin) and represents a spliced form of the other, more abundant transcript (msTmaj). The transcript Tmaj encodes a protein of 264 amino acids, whereas transcripts Tmin and msTmaj encode proteins that are truncated at the N-terminus. All three putative proteins contain a stretch of approximately 90 amino acids, the ribonucleoprotein motif (RNP motif), which shows similarity to a variety of different ribonucleoproteins. Transformation studies reveal that a cDNA corresponding to the transcript Tmaj can provide all the functions for female sex determination and male fertility. Surprisingly, a cDNA corresponding to the transcript msTmaj could only supply some female sex-determining function, but was unable to restore fertility in mutant males. Sequence analysis of two temperature-sensitive mutations provides evidence that the RNP motif represents an important functional domain of the tra-2 protein.

Amino Acid Sequence↗
PubMed1995

Mouse skin tumor progression results in differential expression of retinoic acid and retinoid X receptors.

Retinoids are powerful regulators of epidermal cell growth and differentiation and are widely used in the prevention and treatment of skin disorders and cancers in humans. Since many of the effects of retinoids on cell growth and differentiation are mediated by nuclear retinoid receptors (RARs and RXRs), we were interested in determining RAR and RXR gene expression during mouse skin tumor progression. The two-stage system of mouse skin carcinogenesis was used to generate papillomas and carcinomas, and the different stages of malignant progression (papillomas, differentiated squamous cell carcinomas, undifferentiated squamous cell carcinomas, and spindle cell carcinomas) were characterized in each tumor by specific keratin expression prior to receptor characterization. Using in situ hybridization analysis, we show that the two major RAR isoforms (alpha 1 and gamma 1), which account for most of RARs in the skin, were expressed in both the basal and suprabasal layers in mouse epidermis. In contrast, RXR alpha transcripts were compartmentalized to the basal cell layers and concentrated in hair follicles. During skin tumor progression, RAR (alpha 1 and gamma 1) transcripts were down-modulated in malignant tumor cells, whereas RXR (alpha and beta) transcript expression was expanded in papillomas and carcinomas as the number of undifferentiated cells also increased. RXR gamma was not detected in the skin or at any stage during skin tumor progression. Spindle cell tumors lacked markers of the keratinocyte phenotype and lost RAR expression, yet retained expression of RXR alpha and beta. The increased abundance of transcripts for RXRs and decreased presence of RARs in skin tumor progression may favor other nuclear signal transduction pathways requiring RXR for heterodimer formation and contribute to phenotypic progression of cancer cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2003

Overexpression of transcripts containing LINE-1 in the synovia of patients with rheumatoid arthritis.

OBJECTIVE: To identify novel diagnostic markers by comparing gene expression in rheumatoid (RA) and reactive arthritis (ReA) synovium. METHODS: Synovial biopsy specimens were obtained by needle arthroscopy from the knees of 10 patients with either RA or ReA. RNA was isolated from the biopsy specimens and cDNA synthesised for analysis using a customised cDNA macroarray. Confirmatory analysis was performed using in situ hybridisation on a second set of synovial samples. RESULTS: Two unique transcripts (ReXS1 and fibronectin) were consistently more abundant in ReA and three homologous transcripts were more abundant in RA. The latter all mapped within long interspersed nucleotide elements (LINE-1), that form one of the families of repetitive sequences in the human genome. CONCLUSIONS: The abundance of transcripts containing LINE-1 in the RA synovium may be an epiphenomenon or may have pathogenic significance. Further work is required to determine the identity of the full length transcript(s) before its use as a diagnostic marker in RA can be assessed.

Adolescent↗
PubMed2006

Differential expression of the Bhmp39 major outer membrane proteins of Brachyspira hyodysenteriae.

The enteric, anaerobic spirochete Brachyspira hyodysenteriae is the causative agent of swine dysentery, a severe mucohemorrhagic diarrheal disease of pigs that has economic significance in every major pork-producing country. Recent investigation into potential vaccine candidates has focused on the outer membrane proteins of B. hyodysenteriae. Bhmp39 (formerly Vsp39) is the most abundant surface-exposed outer membrane protein of B. hyodysenteriae; its predicted gene sequence has previously been shown to share sequence similarity to eight genes divided evenly between two paralogous loci. The peptide sequence suggested that Bhmp39 is encoded by one of these genes, bhmp39h. The biological significance of maintaining eight homologous bhmp39 genes is unclear, though it has been proposed that this may play a role in antigenic variation. In this study, real-time, reverse transcription-PCR was used to demonstrate that bhmp39f and bhmp39h were the transcripts most abundantly expressed by B. hyodysenteriae strain B204 cultured under in vitro growth conditions. Mass spectrometry data of the purified 39-kDa membrane protein showed that both Bhmp39f and Bhmp39h were present. Northern blot analysis across predicted Rho-independent terminators demonstrated that the genes of the bhmp39efgh locus result in monocistronic transcripts.

Amino Acid Sequence↗
PubMed1999

Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.

We isolated the human adipose-specific and most abundant gene transcript, apM1 (Maeda, K., et al., Biochem. Biophys. Res. Commun. 221, 286-289, 1996). The apM1 gene product was a kind of soluble matrix protein, which we named adiponectin. To quantitate the plasma adiponectin concentration, we have produced monoclonal and polyclonal antibodies for human adiponectin and developed an enzyme-linked immunosorbent assay (ELISA) system. Adiponectin was abundantly present in the plasma of healthy volunteers in the range from 1.9 to 17.0 mg/ml. Plasma concentrations of adiponectin in obese subjects were significantly lower than those in non-obese subjects, although adiponectin is secreted only from adipose tissue. The ELISA system developed in this study will be useful for elucidating the physiological and pathophysiological role of adiponectin in humans.

Adiponectin↗
PubMed1994

Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells.

X chromosome-linked severe combined immunodeficiency disease (SCIDX1) is characterized by the absence of T-cell and natural killer cell development and results from molecular mutations of the interleukin 2 receptor (IL-2R) gamma chain. The IL-2R gamma chain is a common component of the IL-2, IL-4, and IL-7 receptor systems, which may explain the severe immunophenotype in SCIDX1. We have previously described an atypical SCIDX1 syndrome demonstrating poorly functioning peripheral T cells, which we hypothesized to represent a variant allele at the SCIDX1 locus. We now demonstrate that a splice site mutation in the IL-2R gamma gene is responsible for this atypical SCIDX1. Aberrant RNA splicing resulted in the generation of two IL-2R gamma transcripts: an abundant, nonfunctional isoform containing a small intronic insertion and a second functional isoform with a single amino acid substitution present in limited amounts. Radiolabeled IL-2 binding studies revealed a 5-fold decreased level of expression of functional high-affinity IL-2Rs, which correlated with the quantity of full-length IL-2R gamma transcripts. Further analysis of the T-cell antigen receptor beta-chain repertoire of the patient's T cells demonstrated oligoclonality in multiple V beta families, thus strongly suggesting that the defect in the IL-2R gamma chain generated a limited number of peripheral T-cell clones. This atypical SCIDX1 patient demonstrates that certain IL-2R gamma chain abnormalities can also result in partial immunodeficiency phenotypes, potentially through differential effects on the IL-2, IL-4, or IL-7 receptor systems.

Amino Acid Sequence↗
PubMed1995

Improved accumulation and activity of ribozymes expressed from a tRNA-based RNA polymerase III promoter.

RNA polymerase III (pol III) transcripts are abundant in all cells. Therefore, pol III promoters may be ideal for expressing high levels of exogenous RNAs, such as antisense RNAs, decoy RNAs and ribozymes, in many different cell types. We have improved accumulation of recombinant RNAs expressed from a human meti tRNA-derived pol III promoter > 100-fold by modifying the 3' terminus of the transcripts to hybridize to the 5' terminus. This terminal duplex includes the 8 nt leader sequence present in the primary wild-type meti tRNA transcript that is normally removed during processing to the mature tRNA. Expression of an anti-HIV ribozyme was analyzed in cells stably transduced with retroviral vectors encoding pol III transcription units containing this modification. High accumulation of recombinant pol III ribozyme transcripts was observed in all cell lines tested. Due to the enhanced transcript accumulation, ribozyme cleavage activity was readily detectable in total RNA extracted from stably transduced human T cell lines. One pol III transcription unit, termed 'TRZ', was optimized further for ribozyme cleavage activity. The improved pol III transcription units reported here may be useful for expressing a variety of functional and therapeutic RNAs.

Base Sequence↗
PubMed1995

Expression of the helix-loop-helix gene Id3 during murine embryonic development.

The family of dominant-negative helix-loop-helix (dnHLH) transcriptional modulators consists of four mammalian genes known to date: Id1, Id2, Id3 (Id3 was formerly designated HLH462 or HEIR1 or HLH1R21), and Id4. We have performed a detailed study of Id3 expression in mouse embryos in order to gain insight into the possible developmental control functions of this gene and to compare its expression to that of other mammalian dnHLH genes. Employing RNA in situ hybridization on sectioned mouse embryos of gestational stages E9.5-17.5 and neonatal head, we generally detected a high abundance of transcripts at early stages that gradually declined at most sites toward E15.5. Expression of Id3 in embryos was detected in brain, spinal cord, olfactory system, branchial arches, limbs, sclerotome, endocardiac cushions, the outer lining of the gut, lung, retina, the collecting system of the kidney, and in tooth anlagen. Although the abundance of mRNA decreased toward later stages in most tissues, it remained high in teeth and kidney. This expression pattern suggests that Id3 functions both in undifferentiated tissues and in organs which are in the process of differentiation. When compared to the expression of other dnHLH genes, it becomes obvious that the pattern of Id3 mainly coincides with that of Id1. This may reflect a partial redundancy in gene function. Furthermore, previous experiments suggested a mutually exclusive expression of the proto-oncogene N-myc an Id3. The results of the present study confirm these data.

Animals↗
PubMed2002

Characterization of interactions between RTA and the promoter of polyadenylated nuclear RNA in Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8.

RTA (replication and transcription activator; also referred to as ORF50, Lyta, and ART), an immediate-early gene product of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8, disrupts latency and drives lytic replication. RTA activates the expression of polyadenylated nuclear (PAN) RNA (also known as T1.1 or nut-1) of KSHV. This novel noncoding PAN RNA is the most abundant lytic transcript of KSHV; therefore, studying PAN RNA expression serves as a model system for understanding how RTA transactivates target genes during lytic replication. The RTA-responsive element of the PAN promoter (pPAN RRE) was previously identified, and our data suggested direct binding of full-length RTA to the pPAN RRE. Here, we present a detailed analysis of specific interactions between RTA and the PAN promoter. We expressed and purified the DNA-binding domain of RTA (Rdbd) to near homogeneity and measured its affinity for the pPAN RRE. In electrophoretic mobility shift assays (EMSAs), the dissociation constant (K(d)) of Rdbd on the pPAN RRE was determined to be approximately 8 x 10(-9) M, suggesting a strong interaction between RTA and DNA. The specificity of RTA binding to the PAN promoter was confirmed with supershift assays. The Rdbd binding sequences on the PAN promoter were mapped within a 16-bp region of the pPAN RRE by methylation interference assays. However, the minimal DNA sequence for Rdbd binding requires an additional 7 bp on both sides of the area mapped by interference assays, suggesting that non-sequence-specific as well as sequence-specific interactions between RTA and DNA contribute to high-affinity binding. To better understand the molecular interactions between RTA and the PAN promoter, an extensive mutagenesis study on the pPAN RRE was carried out by using EMSAs and reporter assays. These analyses revealed base pairs critical for both Rdbd binding in vitro and RTA transactivation in vivo of the PAN promoter. The results from methylation interference, deletion analysis, and mutagenesis using EMSAs and reporter assays were closely correlated and support the hypothesis that RTA activates PAN RNA expression through direct binding to DNA.

Base Sequence↗
PubMed2004

Identification of transcripts generated during the response of resistant Biomphalaria glabrata to Schistosoma mansoni infection using suppression subtractive hybridization.

Suppression subtractive hybridization (SSH) was used to construct a complementary DNA library enriched for transcripts more abundantly expressed in the resistant BS90 strain of Biomphalaria glabrata at 12 hr postinfection with Schistosoma mansoni as compared with the susceptible M-line strain under the same circumstances. One hundred and twelve clones of the library were sequenced, yielding 88 unique SSH-expressed sequence tags (ESTs). Differential expression screening indicated that 22 of the 88 unique transcripts were strong candidates for differential expression in the BS90 strain relative to the M-line strain. Analysis of a subset of 4 transcripts using quantitative reverse transcriptase-polymerase chain reaction (qPCR) substantially supports the patterns obtained using the differential expression screen. Furthermore, the qPCR results revealed that gene upregulation in resistant snails, downregulation in susceptible snails, and differences in constitutive gene expression can all account for differential expression during the defense responses of resistant and susceptible snails. The majority (71.6%) of the SSH-ESTs recovered consisted of novel sequences not identified by sequence similarity to known genes. This work complements previous efforts to elucidate the genetic components underlying a successful response to S. mansoni by B. glabrata and identifies a series of transcripts deserving additional study in comparing susceptible and resistant snails.

Analysis of Variance↗
PubMed2026

Hepatitis C Virus Enhances Lysosome-Associated Membrane Protein 2 A Transcription Through Nuclear Factor Erythroid 2-Related Factor 2 to Support Viral Replication.

Hepatitis C virus (HCV) establishes persistent infection by rewiring host stress-response pathways. Chaperone-mediated autophagy (CMA) contributes to HCV replication, but it remains unclear whether HCV regulates lysosome-associated membrane protein 2 A (LAMP-2A), the rate-limiting receptor for CMA. Here, we examined LAMP-2A regulation in HCV-infected Huh-7.5 cells. HCV infection increased LAMP-2A promoter activity, mRNA, and protein abundance, indicating transcriptional upregulation. Among candidate stress-responsive transcription factors, nuclear factor erythroid 2-related factor 2 (NRF2), hypoxia-inducible factor 1α (HIF-1α), and nuclear factor of activated T cells 1 (NFAT1) were elevated in infected cells. However, promoter mutagenesis identified NRF2 as the principal direct regulator. Mutation of the NRF2-responsive antioxidant response element markedly reduced basal and HCV-induced LAMP-2A promoter activity. Chromatin immunoprecipitation assays revealed NRF2 association with the LAMP-2A promoter, and HCV infection increased nuclear accumulation and Ser40 phosphorylation of NRF2. Functionally, shRNA-mediated knockdown of LAMP-2A reduced intracellular HCV RNA and protein levels. These findings identify an NRF2-LAMP-2A regulatory axis engaged during HCV infection and support a model in which HCV upregulates LAMP-2A to establish a cellular environment favorable for viral replication.

Hepacivirus↗
PubMed2002

An alternative internal splicing site defines new Ikaros isoforms in Pleurodeles waltl.

The Ikaros gene encodes a family of transcription factors which plays a crucial role in hematopoiesis. To improve our knowledge about the immune system of Pleurodeles waltl, we sequenced the cDNA coding for the Ik-1 isoform of that salamander and analyzed its tissue expression by semi-quantitative RT-PCR. Ikaros transcripts are abundant in the thymus and the spleen, thereby confirming that these organs are, respectively, the primary and secondary lymphoid tissues of Pleurodeles. Analysis of the isoforms produced by this animal revealed two isoforms characteristic of amphibians in which an alternative internal splicing site deletes the 3' half of exon 3 which interestingly comprises the first Zn finger of Ikaros. Ikaros transcripts were found at the earliest stages of development of Pleurodeles indicating that Ikaros has a function at the very early lymphopoietic stages. Moreover, the presence of Ikaros transcripts in spermatozoa suggests that this protein could have another and yet unknown function.

Alternative Splicing↗
PubMed1998

Molecular, enzymatic, and regulatory characterization of rat kidney cytochromes P450 4A2 and 4A3.

The cDNAs encoding cytochromes CYP 4A2 and 4A3 were cloned by RT-PCR amplification of male rat kidney and liver RNAs, respectively. Sequence analysis demonstrated that these cDNAs were nearly identical to the published sequences for CYPs 4A2 and 4A3. CYP 4A2 and 4A3 share extensive sequence homology that extends into their 3'- and 5'-untranslated segments ( approximately 97% overall nucleotide identity). Analysis of cDNA and genomic DNA sequences shows that a sequence of 123 bp, recognized as an intron during the processing of CYP 4A2 transcripts, is conserved in the 4A3 mRNAs and that these otherwise highly homologous genes show different exon-intron distributions. The CYP 4A2 and 4A3 cDNAs were expressed in a baculovirus-insect cell expression system. Purified recombinant CYP 4A2 oxidized arachidonic acid to a mixture of 19- and 20-hydroxyeicosatetraenoic acids (20 and 80% of the total products, respectively). Reaction rates were maximal when CYP 4A2 was reconstituted in the presence of an equimolar concentration of cytochrome b5 and a 10-fold molar excess of NADPH-cytochrome P450 reductase. Studies using microsomal fractions isolated from noninfected insect cells and from cells infected with CYP 4A3 recombinant baculoviruses showed (a) the presence of an endogenous lauric acid omega-hydroxylase and arachidonic acid epoxygenase in the noninfected cells, (b) the CYP 4A3-dependent oxidation of lauric acid to 11- and 12-hydroxylaurate (24 and 76% of the total products, respectively), and (c) the lack of arachidonic acid metabolism by microsomal recombinant CYP 4A3. Nucleic acid hybridization and immunoelectrophoresis studies demonstrated that (a) CYP 4A2 transcripts are abundantly expressed in the female kidney and that CYP 4A3 is expressed in female but not in male liver, (b) anti-CYP 4A2 immunoreactive material was detected only in the male kidney, (c) male and female livers or kidneys support only low levels of CYP 4A3 translation, and (d) excess dietary salt does not alter the kidney levels of mRNA transcripts encoding CYP 4A1, 4A2, or 4A3 or change the levels of microsomal anti-4A1 or -4A2 immunoreactive proteins. Finally, no significant differences were observed between Dahl salt resistant or Dahl salt sensitive rats in the levels and/or salt regulation of mRNA transcripts enecoding CYP 4A1, 4A2, or 4A3 or the in levels of the corresponding proteins.

Amino Acid Sequence↗
PubMed1999

Structure and developmental expression of Ikaros in the Mexican axolotl.

The Ikaros family of transcription factors plays an essential role in hematopoiesis. We report here the structure of cDNA clones encoding two Ikaros isoforms, Ikl and Ik2, in the Mexican axolotl. The Ik1 cDNA sequence is very similar to that of the rainbow trout, chicken, and mammalian Ik1 sequences. However, a 96 base pair region which encodes the first N-terminal zing finger (F1) is lacking from axolotl Ik1, both in clones from a cDNA library and clones isolated from direct polymerase chain reaction products. A region corresponding to exon 3 is completely absent from the axolotl Ik2 sequence and thus the Ik1 and Ik2 isoforms possess the same number of zinc finger motifs. The structure of these five CC-HH motifs is very well conserved in the axolotl, including the structural deviations from its amino acid consensus composition which are identical in all species analyzed to date. The axolotl Ik1 3' untranslated region sequence is very long (2538 bp) and contains two UA-rich motifs known as instability determinants and which could play a role in mRNA translational efficiency. Ikaros transcripts are first detected in the ventral blood island of stage 36 embryos, about 24 h before the first heartbeats (late tailbud stage), and then in the major lymphopoietic organs of the developing larvae. In situ hybridization demonstrates that Ikaros transcripts are abundant at the periphery of the thymus lobes, in the presumptive site of early thymocyte differentiation.

Ambystoma↗
PubMed1991

Induction of human immunodeficiency virus type 1 expression in chronically infected cells is associated primarily with a shift in RNA splicing patterns.

We have analyzed the kinetics of human immunodeficiency virus type 1 (HIV-1) RNA induction in chronically infected T cells and promonocytes. A substantial amount of spliced mRNAs and assembled virions was found in resting cells. Induction increased the steady-state level of total HIV-1 RNA by 4-fold but increased the level of unspliced transcripts by 25-fold. This increase in unspliced RNA was reflected in the amount of virus seen by electron microscopy. These data suggest a mechanism for the induction of HIV-1 RNA in chronically infected cells involving a shift in splicing greatly favoring the stability of unspliced viral RNA with only a modest increase in total viral RNA. Analysis of the relative abundance of transcript classes is critical to the measurement of HIV-1 viral replication kinetics.

Base Sequence↗