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Molecular and Genetic Analysis of HIV-1
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Molecular and Genetic Analysis of HIV-1

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 15062

Special Issue Editors

Dr. Larance Ronsard

E-Mail Website
Guest Editor
Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA
Interests: sustainability management; sustainability framework; sustainable supply chain; sustainable environmental; sustainable innovation; toxic chemicals, hazardous and radioactive wastes; influenza; HIV-1; AIDS
Special Issues, Collections and Topics in MDPI journals
Dr. Ashraf S. Yousif

E-Mail Website
Guest Editor
Ragon Institute of MGH, MIT and Harvard, 400 Technology Square, Cambridge, MA 02139, USA
Interests: Influenza; AIDS; sustainability management; sustainability framework; sustainable supply chain; toxicology sustainability
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human immunodeficiency virus (HIV) is a global health concern affecting millions of individuals with a wide variety of recombinants currently circulating and affecting various regions of the globe. UNAIDS reported that AIDS has been one of the deadliest infectious diseases in the world, with 2.1 million individuals currently infected. Over the years, clinical trials have been conducted in different locations with the aim of strengthening immune response to protect against HIV; however, there has been no definitive cure. This speaks for the complex nature of HIV, which is characterized by genetic diversity, high mutation rates, and issues of antiretroviral drug toxicity and viral resistance, presenting further obstacles. Numerous molecular analysis reports have demonstrated the importance of studying the molecular mechanism and characterizing the HIV-1 genes in different populations. HIV pathogenesis can also be targeted to induce mutational changes, which can form a defective phenotype of the HIV. These pathophysiology studies, being the central driver for HIV replication, have significance in the future, which can potentially contribute towards designing ideal therapeutics against HIV. Here, in this Special Issue, we invite manuscripts related to HIV-1 vaccines, genetics, epidemiology, and other HIV-1-based research studies/reviews.

Dr. Larance Ronsard
Dr. Ashraf S. Yousif
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • HIV-1
  • Recombinants
  • Vaccines
  • bNAbs
  • AIDS
  • B-cell receptor

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Published Papers (3 papers)

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Research

13 pages, 2028 KiB  
Article
Validation of Promoters and Codon Optimization on CRISPR/Cas9-Engineered Jurkat Cells Stably Expressing αRep4E3 for Interfering with HIV-1 Replication
by Koollawat Chupradit, Kanokporn Sornsuwan, Kritayaporn Saiprayong, Methichit Wattanapanitch and Chatchai Tayapiwatana
Int. J. Mol. Sci. 2022, 23(23), 15049; https://doi.org/10.3390/ijms232315049 - 30 Nov 2022
Cited by 1 | Viewed by 3216
Abstract
Persistent and efficient therapeutic protein expression in the specific target cell is a significant concern in gene therapy. The controllable integration site, suitable promoter, and proper codon usage influence the effectiveness of the therapeutic outcome. Previously, we developed a non-immunoglobulin scaffold, alpha repeat [...] Read more.
Persistent and efficient therapeutic protein expression in the specific target cell is a significant concern in gene therapy. The controllable integration site, suitable promoter, and proper codon usage influence the effectiveness of the therapeutic outcome. Previously, we developed a non-immunoglobulin scaffold, alpha repeat protein (αRep4E3), as an HIV-1 RNA packaging interference system in SupT1 cells using the lentiviral gene transfer. Although the success of anti-HIV-1 activity was evidenced, the integration site is uncontrollable and may not be practical for clinical translation. In this study, we use the CRISPR/Cas9 gene editing technology to precisely knock-in αRep4E3 genes into the adeno-associated virus integration site 1 (AAVS1) safe harbor locus of the target cells. We compare the αRep4E3 expression under the regulation of three different promoters, including cytomegalovirus (CMV), human elongation factor-1 alpha (EF1α), and ubiquitin C (UbC) promoters with and without codon optimization in HEK293T cells. The results demonstrated that the EF1α promoter with codon-optimized αRep4E3mCherry showed higher protein expression than other promoters with non-optimized codons. We then performed a proof-of-concept study by knocking in the αRep4E3mCherry gene at the AAVS1 locus of the Jurkat cells. The results showed that the αRep4E3mCherry-expressing Jurkat cells exhibited anti-HIV-1 activities against HIV-1NL4-3 strain as evidenced by decreased capsid (p24) protein levels and viral genome copies as compared to the untransfected Jurkat control cells. Altogether, our study demonstrates that the αRep4E3 could interfere with the viral RNA packaging and suggests that the αRep4E3 scaffold protein could be a promising anti-viral molecule that offers a functional cure for people living with HIV-1. Full article
(This article belongs to the Special Issue Molecular and Genetic Analysis of HIV-1)
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14 pages, 1175 KiB  
Article
Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil
by Ana Santos-Pereira, Vera Triunfante, Pedro M. M. Araújo, Joana Martins, Helena Soares, Eva Poveda, Bernardino Souto and Nuno S. Osório
Int. J. Mol. Sci. 2021, 22(10), 5304; https://doi.org/10.3390/ijms22105304 - 18 May 2021
Cited by 8 | Viewed by 5226
Abstract
The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We [...] Read more.
The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles. Full article
(This article belongs to the Special Issue Molecular and Genetic Analysis of HIV-1)
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16 pages, 2208 KiB  
Article
Spontaneous Mutations in HIV-1 Gag, Protease, RT p66 in the First Replication Cycle and How They Appear: Insights from an In Vitro Assay on Mutation Rates and Types
by Joshua Yi Yeo, Darius Wen-Shuo Koh, Ping Yap, Ghin-Ray Goh and Samuel Ken-En Gan
Int. J. Mol. Sci. 2021, 22(1), 370; https://doi.org/10.3390/ijms22010370 - 31 Dec 2020
Cited by 11 | Viewed by 5716
Abstract
While drug resistant mutations in HIV-1 are largely credited to its error prone HIV-1 RT, the time point in the infection cycle that these mutations can arise and if they appear spontaneously without selection pressures both remained enigmatic. Many HIV-1 RT mutational in [...] Read more.
While drug resistant mutations in HIV-1 are largely credited to its error prone HIV-1 RT, the time point in the infection cycle that these mutations can arise and if they appear spontaneously without selection pressures both remained enigmatic. Many HIV-1 RT mutational in vitro studies utilized reporter genes (LacZ) as a template to investigate these questions, thereby not accounting for the possible contribution of viral codon usage. To address this gap, we investigated HIV-1 RT mutation rates and biases on its own Gag, protease, and RT p66 genes in an in vitro selection pressure free system. We found rare clinical mutations with a general avoidance of crucial functional sites in the background mutations rates for Gag, protease, and RT p66 at 4.71 × 10−5, 6.03 × 10−5, and 7.09 × 10−5 mutations/bp, respectively. Gag and p66 genes showed a large number of ‘A to G’ mutations. Comparisons with silently mutated p66 sequences showed an increase in mutation rates (1.88 × 10−4 mutations/bp) and that ‘A to G’ mutations occurred in regions reminiscent of ADAR neighbor sequence preferences. Mutational free energies of the ‘A to G’ mutations revealed an avoidance of destabilizing effects, with the natural p66 gene codon usage providing barriers to disruptive amino acid changes. Our study demonstrates the importance of studying mutation emergence in HIV genes in a RT-PCR in vitro selection pressure free system to understand how fast drug resistance can emerge, providing transferable applications to how new viral diseases and drug resistances can emerge. Full article
(This article belongs to the Special Issue Molecular and Genetic Analysis of HIV-1)
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