Mutations in the <i>nef</i> and <i>vif</i> genes associated with progression to AIDS in elite controller and slow‐progressor Patients

Cruz, Nádia Vaez Gonçalves da; Amorim, Raquel Beltrão; Oliveira, Fernando Bernardes de; Speranza, Francisco A.C.; Costa, Luciana Jesus da

doi:10.1002/jmv.23512

Cited by 19 publications

(12 citation statements)

References 52 publications

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“…In conclusion, the finding that the levels of hsa-miR29-3p, hsa-miR-33a-5p and hsa-miR-146a-5p are higher in the plasma of EC than in CH is striking, especially, if considering that miR-29b-3p is known to target Nef373839 and alterations in Nef functions have been associated to slower progression to AIDS4041. Similarly, hsa-miR-146a-5p has been found to target CXCR442 and thus it could affect HIV infection, while no connection of miR-33a and HIV infection has been published so far.…”

Section: Discussionmentioning

confidence: 93%

MicroRNAs differentially present in the plasma of HIV elite controllers reduce HIV infection in vitro

Reynoso

Laufer

Hackl

et al. 2014

Sci Rep

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Elite controllers maintain HIV-1 viral loads below the limit of detection. The mechanisms responsible for this phenomenon are poorly understood. As microRNAs (miRNAs) are regulators of gene expression and some of them modulate HIV infection, we have studied the miRNA profile in plasma from HIV elite controllers and chronically infected individuals and compared against healthy donors. Several miRNAs correlate with CD4+ T cell count or with the known time of infection. No significant differences were observed between elite controllers and healthy donors; however, 16 miRNAs were different in the plasma of chronic infected versus healthy donors. In addition, levels of hsa-miR-29b-3p, hsa-miR-33a-5p and hsa-miR-146a-5p were higher in plasma from elite controllers than chronic infected and hsa-miR-29b-3p and hsa-miR-33a-5p overexpression significantly reduced the viral production in MT2 and primary T CD4+ cells. Therefore, levels of circulating miRNAs might be of diagnostic and/or prognostic value for HIV infection, and hsa-miR-29b-3p and miR-33a-5p may contribute to the design of new anti-HIV drugs.

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Section: Discussionmentioning

confidence: 93%

MicroRNAs differentially present in the plasma of HIV elite controllers reduce HIV infection in vitro

Reynoso

Laufer

Hackl

et al. 2014

Sci Rep

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“…It is worth mentioning that a 40.8 ± 1.7% of inhibition in the luciferase assay is not expected to necessarily correlate with a lack of biological effect of the selected vif -specific shRNA especially in vivo where Vif plays a crucial role. 66,67,68,69,70 Finally, the CCR5 -specific shRNA showed a potent silencing activity independently from the pol-III promoter employed.…”

Section: Discussionmentioning

confidence: 94%

Development of Lentiviral Vectors Simultaneously Expressing Multiple siRNAs Against CCR5, vif and tat/rev Genes for an HIV-1 Gene Therapy Approach

Spanevello

Calistri

Vecchio

et al. 2016

Molecular Therapy - Nucleic Acids

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Gene therapy holds considerable promise for the functional cure of HIV-1 infection and, in this context, RNA interference (RNAi)-based approaches represent powerful strategies. Stable expression of small interfering RNAs (siRNAs) targeting HIV genes or cellular cofactors has the potential to render HIV-1 susceptible cells resistant to infection. To inhibit different steps of virus life cycle, self-inactivating lentiviral vectors expressing multiple siRNAs targeting the CCR5 cellular gene as well as vif and tat/rev viral transcripts, under the control of different RNA polymerase III promoters (U6, 7SK, H1) were developed. The use of a single RNA polymerase III promoter driving the expression of a sequence giving rise to three siRNAs directed against the selected targets (e-shRNA) was also investigated. Luciferase assay and inhibition of HIV-1 replication in human Jurkat T-cell line were adopted to select the best combination of promoter/siRNA. The efficacy of selected developed combinatorial vectors in interfering with viral replication was evaluated in human primary CD4+ T lymphocytes. We identified two effective anti-HIV combinatorial vectors that conferred protection against R5- and X4- tropic viruses. Overall, our results showed that the antiviral effect is influenced by different factors, including the promoter used to express the RNAi molecules and the selected cassette combination. These findings contribute to gain further insights in the design of RNAi-based gene therapy approaches against HIV-1 for clinical application.

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“…Nef Gene Nef protein is involved in HIV progression and expressed in early stages of viral life cycle. Mutations in the nef gene are associated with long-term non-progression of virus in patients [39]. It can be found in the cells as two main isoforms translated by two in-frame translational start codons, p27 (27 kDa), which represent the full-length viral protein and p25 (25 kDa), 18 amino acid truncated form.…”

Section: Hiv (Human Immunodeficiency Virus)mentioning

confidence: 99%

Recombinant Plant Engineering for Immunotherapeutic Production

et al. 2017

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Purpose of Review The requirement for large quantities of therapeutic proteins has fueled a great interest in the production of recombinant proteins in plant bioreactors. The vaccines and bio-therapeutic protein production in plants hold the promise of significantly lowering the cost of manufacturing life-saving drugs. This review will reflect the current status and challenges that the molecular farming platform faces becoming a strategic solution for the development of low-cost bio-therapeutics for developing countries. Recent Findings Different plant parts have been successfully identified as suitable expression systems for the commercial production of therapeutic proteins for some human and animal diseases ranging from common cold to AIDS. The processed therapeutics from such sources are devoid of any toxic components. The large-scale cultivation of these transgenic plants would be possible anywhere in the world including developing countries, which lack sophisticated drug manufacturing units. A couple of such commercially generated products have already hit the market with success. Newer methods using suitable plant viruses and recombinant gene expression systems have already been devised for producing therapeutic proteins and peptides. Summary Plants are promising bio-factories for therapeutic protein production because of their several advantages over the other expression systems especially the advanced mechanisms for protein synthesis and post-translational modification which are very much similar to animal cells. Plant biotechnologists are much attracted to the bio-farming because of its flexibility, scalability, low manufacturing cost, as well as the lack of risk of toxic or pathogenic contamination. A number of projects on bio-farming are designed and are at various developmental stages but have not yet become available to the pharmaceutical industry. Therefore, we need further advancement in the optimization of lab protocols for up-scaling the production of such therapeutics at commercial level with a promise to offer their best clinical use.

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Mutations in the nef and vif genes associated with progression to AIDS in elite controller and slow‐progressor Patients

Cited by 19 publications

References 52 publications

MicroRNAs differentially present in the plasma of HIV elite controllers reduce HIV infection in vitro

MicroRNAs differentially present in the plasma of HIV elite controllers reduce HIV infection in vitro

Development of Lentiviral Vectors Simultaneously Expressing Multiple siRNAs Against CCR5, vif and tat/rev Genes for an HIV-1 Gene Therapy Approach

Recombinant Plant Engineering for Immunotherapeutic Production

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