Human Immunodeficiency Virus Type 2 Multiply Spliced Transcripts

Chatterjee, Pramita; Garzino-Demo, Alfredo; Swinney, P; Arya, Suresh K.

doi:10.1089/aid.1993.9.331

Cited by 10 publications

(9 citation statements)

References 18 publications

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“…Although both motifs are expected to be in close proximity to the cap structure, the much stronger stability of HIV-2 TAR could be responsible for reduced translational efficiency. However, the HIV-2 5′-UTR contains a 140 nt intron that is removed in multiple spliced transcripts (66). Interestingly, Lodmell and colleagues (67) recently showed that this intron could also be removed from the gRNA 5′-UTR resulting in an mRNA with enhanced translation.…”

Section: Resultsmentioning

confidence: 99%

“…To date, it is unknown whether cellular factors participate in the regulation of HIV-2 translation through TAR. However, destabilization of the TAR structure by removal of an intron present within the 5′-UTR (66,67) and the use IRES elements within the Gag coding region (32–35) confers two alternative ways to overcome TAR constraints and allow Gag and Gag-Pol production. Thus, the direct binding of eIF3 and the 40S ribosomal subunit to the Gag IRES (35) may allow the full-length unspliced HIV-2 gRNA to be associated with polysomes.…”

Section: Discussionmentioning

confidence: 99%

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Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation

Soto-Rifo

Limousin

Rubilar

et al. 2011

Nucleic Acids Research

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The 5′-untranslated region (5′-UTR) of the genomic RNA of human immunodeficiency viruses type-1 (HIV-1) and type-2 (HIV-2) is composed of highly structured RNA motifs essential for viral replication that are expected to interfere with Gag and Gag-Pol translation. Here, we have analyzed and compared the properties by which the viral 5′-UTR drives translation from the genomic RNA of both human immunodeficiency viruses. Our results showed that translation from the HIV-2 gRNA was very poor compared to that of HIV-1. This was rather due to the intrinsic structural motifs in their respective 5′-UTR without involvement of any viral protein. Further investigation pointed to a different role of TAR RNA, which was much inhibitory for HIV-2 translation. Altogether, these data highlight important structural and functional differences between these two human pathogens.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation

Soto-Rifo

Limousin

Rubilar

et al. 2011

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Differences between HIV-1 and HIV-2 may also exist following transcriptional initiation. For instance, the HIV-2 LTR is significantly larger than the HIV-1 LTR, has been shown to undergo 5Ј LTR splicing, and has a complex secondary structure that may affect transcriptional trans-activation (4,7). While the exact effect this has on mRNA accumulation in vivo remains unknown, it is possible that differences in the LTR structure result in less-efficient transcriptional elongation and/or the switch from early to late transcripts in HIV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Direct Evidence of Lower Viral Replication Rates In Vivo in Human Immunodeficiency Virus Type 2 (HIV-2) Infection than in HIV-1 Infection

MacNeil

Sarr

Sankalé

et al. 2007

J Virol

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Studies have shown that human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV-1, with a lower rate of disease progression. Similarly, plasma viral loads are lower in HIV-2 infection, suggesting that HIV-2 replication is restricted in vivo in comparison to that of HIV-1. However, to date, in vivo studies characterizing replication intermediates in the viral life cycle of HIV-2 have been limited. In order to test the hypothesis that HIV-2 has a lower replication rate in vivo than HIV-1 does, we quantified total viral DNA, integrated proviral DNA, cell-associated viral mRNA, and plasma viral loads in peripheral blood samples from groups of therapy-naïve HIV-1-infected (n ‫؍‬ 21) and HIV-2-infected (n ‫؍‬ 18) individuals from Dakar, Senegal, with CD4؉ T-cell counts of >200/l. Consistent with our previous findings, total viral DNA loads were similar between HIV-1 and HIV-2 and plasma viral loads were higher among HIV-1-infected individuals. Proportions of DNA in the integrated form were also similar between these viruses. In contrast, levels of viral mRNA were lower in HIV-2 infection. Our study indicates that HIV-2 is able to establish a stable, integrated proviral infection in vivo, but that accumulation of viral mRNA is attenuated in HIV-2 infection relative to that in HIV-1 infection. The differences in viral mRNA are consistent with the differences in plasma viral loads between HIV-1 and HIV-2 and suggest that lower plasma viral loads, and possibly the attenuated pathogenesis of HIV-2, can be explained by lower rates of viral replication in vivo.

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“…The limited homology is particularly evident in the 5Ј untranslated leader sequence: SIV has a significantly longer leader sequence than HIV-1 (33) and it possesses a functional intron within the long terminal repeat (6,10,40,43). For HIV-1, the encapsidation signal has been shown to be composed of at least four stem-loop structures distributed both at the 5Ј and 3Ј ends of the major SD site (1-3, 8, 14, 22, 24, 42).…”

mentioning

confidence: 99%

The Simian Immunodeficiency Virus 5′ Untranslated Leader Sequence Plays a Role in Intracellular Viral Protein Accumulation and in RNA Packaging

Patel

Wang

Izmailova

et al. 2003

J Virol

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We investigated the role of 5 untranslated leader sequences of simian immunodeficiency virus (SIV mac239 ) in RNA encapsidation and protein expression. A series of progressively longer deletion mutants was constructed with a common endpoint six nucleotides upstream of the gag initiation codon and another endpoint at the 3 end of the primer binding site (PBS). We found that efficient intracellular Gag-Pol protein accumulation required the region between the PBS and splice donor (SD) site. Marked reduction of genomic RNA packaging was observed with all the deletion mutants that involved sequences at both the 5 and at the 3 ends of the major SD site, and increased nonspecific RNA incorporation could be detected in these mutants. RNA encapsidation was affected only modestly by a deletion of 54 nucleotides at the 3 end of the SD site when the mutant construct p⌬54 was transfected alone. In contrast, the amount of p⌬54 genomic RNA incorporated into particles was reduced more than 10-fold when this mutant was cotransfected with a construct specifying an RNA molecule with a wild-type packaging signal. Therefore, we conclude that the 175 nucleotides located 5 of the gag initiation codon are critical for efficient and selective incorporation of genomic RNA into virions. This location of the SIV ⌿ element provides the means for efficient discrimination between viral genomic and spliced RNAs.The 5Ј untranslated leader of retroviruses is involved in a variety of functions that affect different steps of the retrovirus life cycle. Among these are RNA elongation, RNA splicing, protein translation, genomic RNA dimerization and packaging, and initiation of reverse transcription (5,9,17,18,24,27,29). While RNA elongation, RNA splicing, and initiation of reverse transcription are associated with short and well-defined sequences, RNA translation and packaging elements are distributed over longer sequences that are less well defined in length and structure.Packaging of retroviral RNAs involves the selective encapsidation of an unspliced genomic RNA dimer into the virion (12, 34). For many retroviruses, critical portions of the packaging signal (⌿) have been mapped between the major splice donor (SD) site and the gag initiation codon (12,34). This location of ⌿ permits discrimination between full-length genomic RNA and subgenomic RNA species during the packaging process (25,32,37). RNA incorporation occurs via interactions between the cis-acting elements, which are located in the 5Ј untranslated RNA leader, and the trans-acting

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Human Immunodeficiency Virus Type 2 Multiply Spliced Transcripts

Cited by 10 publications

References 18 publications

Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation

Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation

Direct Evidence of Lower Viral Replication Rates In Vivo in Human Immunodeficiency Virus Type 2 (HIV-2) Infection than in HIV-1 Infection

The Simian Immunodeficiency Virus 5′ Untranslated Leader Sequence Plays a Role in Intracellular Viral Protein Accumulation and in RNA Packaging

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