HIV-1 Unique Recombinant Forms Identified in Slovenia and Their Characterization by Near Full-Length Genome Sequencing

Lunar, Maja M.; Mlakar, Jana; Zorec, Tomaž Mark; Poljak, Mario

doi:10.3390/v12010063

Cited by 7 publications

(7 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…11 Since the first case of HIV was reported, other predominant HIV subtypes are slowly becoming prevalent in Pakistan. 12 Our study reported that a few sequences were clustering with subtype B, similar to a recently published study that revealed 9.5% of sequences from the database were closely pressing with subtype B. 13 Our study also reveals that 6.25% of sequences clustered with CRF02_AG.…”

Section: Discussionsupporting

confidence: 88%

Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan

Zahid

Khan²,

Qureshi³

et al. 2022

Pak J Med Sci

View full text Add to dashboard Cite

Background and Objective: Pakistan has witnessed a dramatic change in the increasing prevalence and emergence of HIV subtypes for more than two decades. Pakistani population is increasingly engaged in high-risk practices, and the prescribed drugs are potentially causing resistance. There are chances that these resistant strains are beginning to circulate from high-risk to the general population. Methods: The study was conducted at the section of Molecular Pathology Lab of Dow Diagnostic and Research Laboratory, Dow University of Health Sciences (DUHS) Karachi. In this study, we analyzed gene sequences of HIV for drug resistance and molecular epidemiology., along with amino acid sequence variability. Furthermore, we undertook phylogenetic analysis for possible geographic linkages of Pakistani HIV strains. Results: Our results demonstrate that A1 is the leading HIV subtype circulating in the country, whereas other emerging subtypes and recombinant forms, including subtype B, CRF02_AG, CRF10_CD CRF35_AD, and CRF11_cpx were also observed. Our sequences cluster with the Middle East, African, and a few European sequences according to geographical distribution. These sequences showed high-level resistance per drug resistance pattern, with 62.5% of patients exhibiting resistance to NNRTI drugs and 60% mutation at E138A and K103N, respectively, against NNRTI drugs. About 75% sequences showed resistance mutation at M184V against NRTI drugs. The antiretroviral drugs are now causing H-LR to the patients with no effect. Our results also revealed that certain regions of RT exhibited high sequence variability, especially at Amino Acids positions p.119, p.130, p.157, p.164. Conclusion: We hereby report major novel mutations and several minor mutations that may have a drastic change in the drug resistance pattern. doi: https://doi.org/10.12669/pjms.38.7.5591 How to cite this:Zahid M, Khan S, Qureshi MA, Raza Y. Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan. Pak J Med Sci. 2022;38(7):1857-1863. doi: https://doi.org/10.12669/pjms.38.7.5591 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

show abstract

Section: Discussionsupporting

confidence: 88%

Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan

Zahid

Khan²,

Qureshi³

et al. 2022

Pak J Med Sci

View full text Add to dashboard Cite

show abstract

“…However, the gold standard for HIV-1 classification remains phylogenetic analysis of full-length genome sequences, which was out of the scope of our study (32). Indeed, some of the unresolved sequences from this study were further investigated with detailed whole genome analyses in another study (29). However, we cannot rule out the possibility that the sequences resolved as specific subtypes or CRFs in this study belong to other subtypes in other regions of the genome that were not sequenced.…”

Section: Discussionmentioning

confidence: 90%

“…However, because only part of the pol region was studied, the diversity among Slovenian sequences could be much higher. The unresolved sequences were further investigated with detailed whole genome analyses (29).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

HIV-1 subtype diversity and phylogenetic insight into non-B subtype transmission in Slovenia, 1989-2013

Mlakar,

Lunar,

Abecasis

et al. 2023

Acta Dermatovenerologica Alpina Pannonica Et Adriatica

View full text Add to dashboard Cite

Introduction: Disease progression, drug resistance mutations, and treatment strategies may vary by HIV-1 subtype. This study determined HIV-1 subtypes circulating in Slovenia, a Central European country with an HIV-1 epidemic driven by men who have sex with men, focusing on molecular epidemiology of non-B subtypes. Methods: A total of 367 HIV-1 sequences were included. Subtype was assigned by employing eight different HIV subtyping tools coupled with maximum likelihood phylogenetic analyses. Results: The subtyping tools COMET, jpHMM, and REGA 3.0 exhibited the best performance on the dataset studied. Phylogenetic analyses showed a 14.7% prevalence of non-B subtypes, with subtype A detected most frequently (4.9%), followed by CRF02_AG (2.4%), subtype C (1.1%), subtypes D, G, and CRF01_AE (0.8% each), and subtypes F and CRF22_01A1 (0.3% each). A subtype could not be assigned to 12 sequences (3.3%), indicating potential unique recombinant forms. Non-B subtypes were significantly associated with a heterosexual route of transmission and infection acquired in Eastern Europe, Africa, or Asia. Conclusions: In a country where subtype B is predominant, non-B subtypes were observed in one out of seven patients, a nonnegligible proportion, which underlines the importance of systematic surveillance of HIV subtype diversity and the corresponding molecular epidemiology.

show abstract

“…This phenomenon of discrepant subtyping results generated by different subtyping tools was previously exploited in a study for the selection of samples for the characterization of new recombinant HIV-1 strains as novel URFs [ 30 ]. In fact, in this study, REGA HIV-1 and 2 Automated Subtyping Tool Version 2.0 (REGA 2.0) [ 31 ] and, to a somewhat lesser degree, REGA 3.0 were discovered to perform better than other tools when giving an indication of a possible URF.…”

Section: Discussionmentioning

confidence: 99%

Comparative HIV-1 Phylogenies Characterized by PR/RT, Pol and Near-Full-Length Genome Sequences

Topcu

Georgiou

Rodosthenous

et al. 2022

Viruses

View full text Add to dashboard Cite

In an effort to evaluate the accuracy of HIV-1 phylogenies based on genomes of increasing length, we developed a comprehensive near-full-length HIV-1 genome RT–PCR assay and performed a comparative evaluation via phylogenetic analyses. To this end, we conducted comparative analyses of HIV-1 phylogenies derived based on HIV-1 PR/RT (2253–3359 in the HXB2 genome) and pol region (2253–5250 in the HXB2 genome) sequences isolated from 134 HIV-1-infected patients in Cyprus (2017–2019). The HIV-1 genotypic subtypes determined using six subtyping tools (REGA 3.0, COMET 2.3, jpHMM, SCUEAL, Stanford, and Geno2pheno) were compared to investigate the discrepancies generated among different tools. To evaluate the accuracy of defined HIV-1 phylogenies, the samples exhibiting at least one discrepant subtyping result among different subtyping tools in both PR/RT and pol regions or only in the pol region (n = 38) were selected for near-full-length HIV-1 genome (790–8795 in HXB2 genome) sequencing using a newly developed RT–PCR/sequencing assay. The obtained sequences were employed for HIV-1 genotypic subtype determination and subjected to comparative phylogenetic-based analyses. It was observed that 39.6% of the 134 samples presented discrepancies in the PR/RT region, while 28.4% presented discrepancies in the pol region. REGA 3.0 produced the fewest discrepancies collectively in both regions and was selected for subsequent subtyping and comparative phylogenetic analyses of near-full-length HIV-1 genome sequences. The analyses of near-full-length HIV-1 genome sequences identified 68.4% of the 38 ‘discrepant samples’ (n = 26) as belonging to uncharacterized recombinant HIV-1 strains, while 21.1% were circulating recombinant forms (CRFs) (n = 8) and 10.5% belonged to pure group M subtypes (n = 4). The findings demonstrated a significant reduction of 11.2% in discrepancies when pol region sequences were used compared to PR/RT region sequences, indicating that increased nucleotide sequence lengths are directly correlated with more consistent subtype classification. The results also revealed that if the discrepancy in pol region subtyping results persists, then there is a high likelihood (89.5%) that the query sequence is a recombinant HIV-1 strain, 68.4% of which belong to uncharacterized recombinant HIV-1 strains. The results of this study showed that REGA 3.0 presented the best performance in subtyping recombinant HIV-1 strains, while Stanford performed better in defining phylogenies of pure group M subtypes. The study highlights that, especially in populations with polyphyletic HIV-1 epidemics resulting in a high prevalence of recombinant HIV-1 strains, neither PR/RT nor pol region sequences are reliable for the determination of HIV-1 genotypic subtypes in samples showing discrepancies among different subtyping tools, and only near-full-length or full-length HIV-1 genome sequences are sufficiently accurate.

show abstract

HIV-1 Unique Recombinant Forms Identified in Slovenia and Their Characterization by Near Full-Length Genome Sequencing

Cited by 7 publications

References 48 publications

Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan

Subgenomic sequence analysis reveals emergence of new circulating recombinant forms of HIV-1 in Pakistan

HIV-1 subtype diversity and phylogenetic insight into non-B subtype transmission in Slovenia, 1989-2013

Comparative HIV-1 Phylogenies Characterized by PR/RT, Pol and Near-Full-Length Genome Sequences

Contact Info

Product

Resources

About