Variable Sequences in the Long Terminal Repeat and Its Downstream Region of Some of HIV Type 1 CRF01_AE Recently Distributing among Thai Carriers

Kurosu, Takeshi; Mukai, T.; Auwanit, Wattana; Ayuthaya, Panasda Isarangkura Na; Saeng-Aroon, Siriphan; Ikuta, Kazuyoshi

doi:10.1089/088922201750252061

Cited by 11 publications

(18 citation statements)

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“…In our study, the Tat activity of subtypes B and E Tat in the mouse NIH3T3 cells was affected by the substitution of amino acid Cys 31 to Ser 31 . In contrast, the substitution of amino acid Ser 31 to Cys 31 in C-Tat did not affect its activity. However, the substitutions of four cysteine residues in this motif almost completely reduced the Tat activities not only in subtypes B and E but also in subtype C (data not shown).…”

Section: Discussionmentioning

confidence: 68%

“…Together, these results suggest that the cysteine-rich motif in C-Tat is important for interaction to human cyclin T1. However, the substitution of Cys 31 to Ser 31 was unlikely to be effectively involved in the bind- ing to cyclin T1 and this is in contrast to that in B-and ETat. Thus, the substitution of Cys 31 to Ser 31 in subtype C was not the major reason for the higher transactivity of CTat.…”

Section: No Involvement Of a Cysteine-rich Motif And 2nd Exon Of Tat mentioning

confidence: 87%

“…The purified PCR products were used as primer sets with T3, T4 and T5, respectively, for the generation of B-Tat containing Ser 31 , C-Tat containing Cys 31 and E-Tat containing Ser 31 , respectively. The sequences of these plasmids were confirmed with ABI 377 (Perkin-Elmer Applied Biosystems, Foster City, Calif., U.S.A.) using the dideoxy nucleotide chain termination method.…”

Section: Methodsmentioning

confidence: 99%

“…3, similar results were obtained by pLTR-Luc derived from subtype E and C LTR sequences (data not shown). When we constructed the mutant Tat with serine in place of Cys 27 , Cys 30 , Cys 31 , and Cys 34 , it was found that the resultant Tats including C-Tat similarly lost their activities in Jurkat cells (data not shown). Together, these results suggest that the cysteine-rich motif in C-Tat is important for interaction to human cyclin T1.…”

Section: No Involvement Of a Cysteine-rich Motif And 2nd Exon Of Tat mentioning

confidence: 99%

“…Subtype C viruses have three or four sites of the NF-κB enhancer element in LTR, unlike subtypes B and E having only two and one, respectively (15,23,25,31,40,41). This difference was shown by transfection assay in HeLa cells to lead to higher promoter/enhancer activities of subtype C LTR (C-LTR) than those of the other subtypes such as B and E (45).…”

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confidence: 99%

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Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Kurosu

Mukai

Komoto

et al. 2002

Microbiology and Immunology

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Although human immunodeficiency virus type 1 (HIV‐1) subtypes C and E are expanding faster and seem to be of greater global significance than HIV‐1 subtype B, there is only little information about Tat activity of such non‐B subtypes. Here, we showed evidence that subtype C Tat exhibits higher transcriptional activity from the HIV‐1 long‐terminal repeat (LTR) in a human T‐cell line, compared with subtypes B and E. This higher activity of subtype C Tat was not due to the LTR, but to the Tat sequence variability. We examined three candidate regions with sequence for the higher activity of subtype C Tat, such as the cysteine‐rich motif, the basic domain, and the 2nd exon. The results showed that the variation in subtype C Tat at two amino acid residues, Ser57 and Glu63 in stead of Arg57 and Gln63 in subtypes B and E, within and close to the basic domain were involved in the higher activity of subtype C Tat. This variation did not affect its nuclear localization activity. Thus, there may be a significant advantage for the high Tat activity on subtype C replication.

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Section: Discussionmentioning

confidence: 68%

Section: No Involvement Of a Cysteine-rich Motif And 2nd Exon Of Tat mentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: No Involvement Of a Cysteine-rich Motif And 2nd Exon Of Tat mentioning

confidence: 99%

mentioning

confidence: 99%

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Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Kurosu

Mukai

Komoto

et al. 2002

Microbiology and Immunology

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Genetic Variation and HIV-Associated Neurologic Disease

Dahiya¹,

Irish²,

Nonnemacher³

et al. 2013

Advances in Virus Research

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HIV-associated neurologic disease continues to be a significant complication in the era of highly active antiretroviral therapy. A substantial subset of the HIV-infected population shows impaired neuropsychological performance as a result of HIV-mediated neuroinflammation and eventual central nervous system (CNS) injury. CNS compartmentalization of HIV, coupled with the evolution of genetically isolated populations in the CNS, is responsible for poor prognosis in patients with AIDS, warranting further investigation and possible additions to the current therapeutic strategy. This chapter reviews key advances in the field of neuropathogenesis and studies that have highlighted how molecular diversity within the HIV genome may impact HIV-associated neurologic disease. We also discuss the possible functional implications of genetic variation within the viral promoter and possibly other regions of the viral genome, especially in the cells of monocyte–macrophage lineage, which are arguably key cellular players in HIV-associated CNS disease.

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Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms

Mbondji-Wonje

Dong

Zhao

et al. 2020

Sci Rep

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The critical role of the regulatory elements at the 5′ end of the HIV-1 genome in controlling the life cycle of HIV-1 indicates that this region significantly influences virus fitness and its biological properties. In this study, we performed a detailed characterization of strain-specific variability of sequences from the U5 to upstream of the gag gene start codon of diverse HIV-1 strains by using next-generation sequencing (NGS) techniques. Overall, we found that this region of the HIV-1 genome displayed a low degree of intra-strain variability. On the other hand, inter-strain variability was found to be as high as that reported for gag and env genes (13-17%). We observed strain-specific single point and clustered mutations in the U5, PBS, and gag leader sequences (GLS), generating potential strainspecific transcription factor binding sites (TFBS). Using an infrared gel shift assay, we demonstrated the presence of potential TFBS such as E-box in CRF22_01A, and Stat 6 in subtypes A and G, as well as in their related CRFs. The strain-specific variation found in the sequence corresponding at the RNA level to functional domains of the 5ʹ UTR, could also potentially impact the secondary/tertiary structural rearrangement of this region. Thus, the variability observed in this 5′ end of the genomic region of divergent HIV-1 strains strongly suggests that functions of this region might be affected in a strain-specific manner. Our findings provide new insights into DNA-protein interactions that regulate HIV-1 replication and the influence of strain characterization on the biology of HIV-1 infection. Human immunodeficiency virus type 1 (HIV-1) is characterized by extensive genetic diversity. HIV-1 group M, which accounts for the majority of infections worldwide, has been subdivided into at least nine genetically distinct subtypes (A-D, F-H, J, and K), a few sub-subtypes (A1-A3, F1, F2), and numerous circulating and unique recombinant forms (CRFs and URFs respectively). HIV-1 diversity is featured by high mutagenesis rates and recombination events occurring during the life cycle of the virus. Nucleotide changes generated from these mechanisms affect the entire viral genome, including its highly structured 5′ end region. Indeed, the HIV-1 genome variability was found to be as much as 23% in the 5′LTR-U3 region, about 10% in the gag/pol genes, and more than 30% in the env gene, with overall differences observed primarily between intra and inter-subtype 1,2. Previous studies have revealed that strain differences may influence transmission, replication, and virulence of HIV-1. It was reported that CRF01_AE has a higher rate of sexual transmission than subtype B 3 , while this rate was higher in subtype A compared to D 4. Subtype A was also shown to have a lower replication rate than subtype C 5 , and a lower rate of disease progression than its related CRFs and subtype D 4. Association of these

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Variable Sequences in the Long Terminal Repeat and Its Downstream Region of Some of HIV Type 1 CRF01_AE Recently Distributing among Thai Carriers

Cited by 11 publications

References 14 publications

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Human Immunodeficiency Virus Type 1 Subtype C Exhibits Higher Transactivation Activity of Tat than Subtypes B and E

Genetic Variation and HIV-Associated Neurologic Disease

Genetic variability of the U5 and downstream sequence of major HIV-1 subtypes and circulating recombinant forms

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