scholarly journals Sequence Length of HIV-1 Subtype B Increases Over Time: Analysis of a Cohort of Patients With Hemophilia Over 30 Years

2021 ◽  
Author(s):  
Young-Keol Cho ◽  
Jung-Eun Kim ◽  
Brian Foley
Keyword(s):  
Direct Sequencing ◽  
Sequence Length ◽  
Coding Region ◽  
Rt Pcr ◽  
Variable Regions ◽  
Subtype B ◽  
Combined Antiretroviral Therapy ◽  
Signature Pattern ◽  
Hiv 1 ◽  
Over Time

We aimed to investigate whether the sequence length of HIV-1 increases over time. A longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among pa-tients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB) was performed. Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis for the KSB of HIV-1 revealed 91 signature nucleotide residues (1.05%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Only six positions contained 100% specific nucleotide(s) in clusters O and P. Additionally, in-depth FL analysis over 30 years indicates that the KSB FL significantly increased over time before combined antiretroviral therapy (cART) and decreased with cART. The increase occurred due to a significant increase in env and nef genes, originating in the variable regions of both genes. The increase in the sequence length of HIV-1 over time suggests that it has an evolutionary direction.

scholarly journals Sequence Length of HIV-1 Subtype B Increases over Time: Analysis of a Cohort of Patients with Hemophilia over 30 Years

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 806
Author(s):  
Young-Keol Cho ◽  
Jung-Eun Kim ◽  
Brian T. Foley
Keyword(s):  
Direct Sequencing ◽  
Sequence Length ◽  
Coding Region ◽  
Rt Pcr ◽  
Time Analysis ◽  
Variable Regions ◽  
Subtype B ◽  
Signature Pattern ◽  
Hiv 1 ◽  
Over Time

We aimed to investigate whether the sequence length of HIV-1 increases over time. We performed a longitudinal analysis of full-length coding region sequences (FLs) during an HIV-1 outbreak among patients with hemophilia and local controls infected with the Korean subclade B of HIV-1 (KSB). Genes were amplified by overlapping RT-PCR or nested PCR and subjected to direct sequencing. Overall, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Phylogenetic analysis indicated that within KSB, two FLs from plasma donors O and P comprised two clusters, together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis of the KSB of HIV-1 revealed 91 signature nucleotide residues (1.1%). In total, 48 and 43 signature nucleotides originated from clusters O and P, respectively. Six positions contained 100% specific nucleotide(s) in clusters O and P. In-depth FL analysis for over 30 years indicated that the KSB FL significantly increased over time before combination antiretroviral therapy (cART) and decreased with cART. This increase occurred due to the significant increase in env and nef genes, originating in the variable regions of both genes. The increase in sequence length of HIV-1 over time suggests an evolutionary direction.

Sequence Length of HIV-1 Subtype B Increases Over Time: Analyzing a Cohort of Patients with Hemophilia Over 30 Years

2021 ◽  
Author(s):  
Young-Keol Cho ◽  
Jung-eun Kim ◽  
Brian Foley
Keyword(s):  
Direct Sequencing ◽  
National Laboratory ◽  
Sequence Length ◽  
Coding Region ◽  
Los Alamos National Laboratory ◽  
Subtype B ◽  
Combined Antiretroviral Therapy ◽  
Signature Pattern ◽  
Hiv 1 ◽  
Over Time

The objective of this study is to investigate whether the sequence length of HIV-1 increases over time. A longitudinal analysis of full-length coding region sequences (FLs) in an outbreak of HIV-1 infection among patients with hemophilia and local controls identified as infected with the Korean subclade B of HIV-1 (KSB). Genes amplified by overlapping RT-PCR or nested PCR were subjected to direct sequencing. In total, 141 FLs were sequentially determined over 30 years in 62 KSB-infected patients. Non-KSB sequences were retrieved from the Los Alamos National Laboratory HIV Database. Phylogenetic analysis indicated that within KSB, 2 FLs from plasma donors O and P comprised two clusters together with 8 and 12 patients with hemophilia, respectively. Signature pattern analysis for the KSB of HIV-1 revealed signature nucleotide residues at 1.05%, compared with local controls. Additionally, in-depth FLs sequence analysis over 30 years in KSB indicates that the KSB FL significantly increases over time before combined antiretroviral therapy (cART) and decreases on cART. Furthermore, the increase in FLs over time significantly occurred in the subtypes B, C and G, but, there was no increase in the subtypes D, A, and F1. Consequently, subtypes F1 and D had the shortest sequence length. Our analysis was extended to compare HIV-1 with HIV-2 and SIVs. Essentially, the longer the sequence length (SIVsm > HIV-2 > SIVcpz > HIV-1), the longer the survival period. The increase in the length of the HIV-1 sequence over time suggests that it might be an evolutionary direction toward attenuated pathogenicity.

scholarly journals Genetic Analysis of the Full-Length gag Gene from the Earliest Korean Subclade B of HIV-1: An Outbreak among Korean Hemophiliacs

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 545 ◽  
Author(s):  
Young-Keol Cho ◽  
Jung-Eun Kim ◽  
Brian T. Foley
Keyword(s):  
Genetic Analysis ◽  
Pattern Analysis ◽  
Direct Sequencing ◽  
Factor Ix ◽  
Full Length ◽  
Clotting Factor ◽  
Gene Sequences ◽  
Subtype B ◽  
Signature Pattern ◽  
Hiv 1

We determined the earliest full-length HIV-1 gag gene sequences in 110 patients with HIV-1, including 20 hemophiliacs (HPs) and 90 local controls (LCs). The gag gene from stored sera was amplified using RT-PCR, and was subjected to direct sequencing. Phylogenetic analysis indicated that 94 and 16 sequences belonged to the Korean subclade of HIV-1 subtype B (KSB) and subtype B, respectively. A total of 12 signature pattern amino acids were found within the KSB, distinct from the worldwide consensus of subtype B. Within the KSB, the gag gene sequences from donors O and P and those from the 20 HPs comprised two subclusters. In particular, sequences from donor O strongly clustered with those of eight HPs. Moreover, signature pattern analysis indicated that 14 signature nucleotides were shared between the HPs and LCs within KSB (p < 0.01). Among the 14 nucleotides, positions 9 and 5 belonged to clusters O and P, respectively. In conclusion, signature pattern analysis for the gag gene revealed 12 signature pattern residues within the KSB and also confirmed the previous conclusion that the 20 HPs were infected with viruses due to incompletely inactivated clotting factor IX. This study is the first genetic analysis of the HIV-1 gag gene in Korea.

scholarly journals Molecular Epidemiology of HIV-1 Infected Migrants Followed Up in Portugal: Trends between 2001–2017

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 268 ◽  
Author(s):  
Victor Pimentel ◽  
Marta Pingarilho ◽  
Daniela Alves ◽  
Isabel Diogo ◽  
Sandra Fernandes ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Molecular Epidemiology ◽  
Nucleoside Reverse Transcriptase Inhibitor ◽  
Country Of Origin ◽  
Transcriptase Inhibitor ◽  
Subtype B ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1 ◽  
Over Time

Migration is associated with HIV-1 vulnerability. Objectives: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. Results: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. Conclusions: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.

A simple competitive RT-PCR assay for quantitation of HIV-1 subtype B and non-B RNA in plasma

2007 ◽  
Vol 142 (1-2) ◽  
pp. 113-117 ◽  
Author(s):  
Makiko Hamatake ◽  
Masako Nishizawa ◽  
Naoki Yamamoto ◽  
Shingo Kato ◽  
Wataru Sugiura
Keyword(s):  
Rt Pcr ◽  
Pcr Assay ◽  
Subtype B ◽  
Hiv 1

scholarly journals Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic

2015 ◽  
Vol 90 (3) ◽  
pp. 1244-1258 ◽  
Author(s):  
Natalie N. Kinloch ◽  
Daniel R. MacMillan ◽  
Anh Q. Le ◽  
Laura A. Cotton ◽  
David R. Bangsberg ◽  
...  
Keyword(s):  
North America ◽  
North American ◽  
Consensus Sequence ◽  
Hla Class I ◽  
Class I ◽  
Recent Common Ancestor ◽  
Most Recent Common Ancestor ◽  
Subtype B ◽  
Hiv 1 ◽  
Over Time

ABSTRACTHuman leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989;n= 338) and modern (2001 to 2011;n= 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ∼2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era.IMPORTANCEHLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may accumulate in circulation over time, potentially undermining host antiviral immunity to the transmitted viral strain. We studied >600 experimentally collected HIV-1 polymerase sequences linked to host HLA information dating back to 1979, along with phylogenetically reconstructed HIV-1 sequences dating back to the virus' introduction into North America. Overall, our results support the gradual spread of many—though not all—HIV-1 polymerase immune escape mutations in circulation over time. This is consistent with recent observations from other global regions, though the extent of polymorphism accumulation in North America appears to be lower than in populations with high seroprevalence, older epidemics, and/or limited HLA diversity. Importantly, the risk of acquiring an HIV-1 polymerase sequence at transmission that is substantially preadapted to one's HLA profile remains relatively low in North America, even in the present era.

HIV-1 Subtype C Drug-Resistance Background among ARV-Naive Adults in Botswana

2005 ◽  
Vol 16 (2) ◽  
pp. 103-115 ◽  
Author(s):  
Hermann Bussmann ◽  
Vladimir Novitsky ◽  
William Wester ◽  
Trevor Peter ◽  
Kereng Masupu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Population Level ◽  
Resistance Mutations ◽  
Subtype C ◽  
Coding Region ◽  
Drug Pressure ◽  
Phenotypic Properties ◽  
Subtype B ◽  
Protease Enzyme ◽  
Hiv 1

Current HIV-1 antiretroviral (ARV) drug resistance knowledge is limited to HIV-1 subtype B (HIV-1B). We addressed whether unique genetic and phenotypic properties of HIV-1 subtype C (HIV-1C), southern Africa's most prevalent subtype, may foment earlier and/or distinct resistance mutations. Population-level HIV-1C genotypes were evaluated with respect to drug resistance prevalence before Botswana's public ARV treatment programme began. Viruses were genotyped from 11 representative districts of northern and southern Botswana, and consensus sequences from these 71 individuals and 51 previously reported sequences from HIV-positive blood donors were constructed. Phylogenetic analysis classified all 71 sequences but one, which exhibited pol gene mosaicism, as HIV-1C. The protease and reverse transcriptase coding region had no detectable known primary mutations associated with HIV-1B protease inhibitor (PI) drug resistance. Secondary mutations associated with PI drug resistance were found in all sequences. Several HIV-1C—specific polymorphic sites were found across the pol gene. Northern and southern Botswana viral sequences showed no significant differences from each other. Population genotyping shows that, without countrywide ARV treatment, HIV-1C—infected Batswana harbour virtually no primary mutations known to confer resistance to the three major HIV-1B ARV drug classes. Some secondary PI mutations and polymorphic sites in the protease enzyme necessitate continuous population monitoring, particularly after introduction of countrywide ARV treatment in Botswana. Although its PI resistance development rate and kinetics are not known, our data may suggest increased susceptibility and readiness of HIV-1C to develop resistance under drug pressure when the PI class of drugs is used.

scholarly journals HIV-1 Group O Integrase Displays Lower Enzymatic Efficiency and Higher Susceptibility to Raltegravir than HIV-1 Group M Subtype B Integrase

2014 ◽  
Vol 58 (12) ◽  
pp. 7141-7150 ◽  
Author(s):  
Agnès Depatureaux ◽  
Peter K. Quashie ◽  
Thibault Mesplède ◽  
Yingshan Han ◽  
Hannah Koubi ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Competitive Inhibition ◽  
Strand Transfer ◽  
Coding Region ◽  
Long Terminal Repeats ◽  
Enzymatic Function ◽  
Subtype B ◽  
The Impact ◽  
Divergent Strain ◽  
Hiv 1

ABSTRACTHIV-1 group O (HIV-O) is a rare HIV-1 variant characterized by a high number of polymorphisms, especially in the integrase coding region. As HIV-O integrase enzymes have not previously been studied, our aim was to assess the impact of HIV-O integrase polymorphisms on enzyme function and susceptibility to integrase inhibitors. Accordingly, we cloned and purified integrase proteins from each of HIV-1 group O clades A and B, an HIV-O divergent strain, and HIV-1 group M (HIV-M, subtype B), used as a reference. To assess enzymatic function of HIV-O integrase, we carried out strand transfer and 3′ processing assays with various concentrations of substrate (DNA target and long terminal repeats [LTR], respectively) and characterized these enzymes for susceptibility to integrase strand transfer inhibitors (INSTIs) in cell-free assays and in tissue culture, in the absence or presence of various concentrations of several INSTIs. The inhibition constant (Ki) and 50% effective concentration (EC50) values were calculated for HIV-O integrases and HIV-O viruses, respectively, and compared with those of HIV-M. The results showed that HIV-O integrase displayed lower activity in strand transfer assays than did HIV-M enzyme, whereas 3′ processing activities were similar to those of HIV-M. HIV-O integrases were more susceptible to raltegravir (RAL) in competitive inhibition assays and in tissue culture than were HIV-M enzymes and viruses, respectively. Molecular modeling suggests that two key polymorphic residues that are close to the integrase catalytic site, 74I and 153A, may play a role in these differences.

scholarly journals Phylogenetic measures of indel rate variation among the HIV-1 group M subtypes

2018 ◽  
Author(s):  
John Palmer ◽  
Art Poon
Keyword(s):  
Sequence Data ◽  
Poisson Model ◽  
Nucleotide Composition ◽  
Rate Variation ◽  
Flanking Sequence ◽  
Nucleotide Substitutions ◽  
Virus Surface ◽  
Variable Regions ◽  
Subtype B ◽  
Hiv 1

The transmission and pathogenesis of human immunodeficiency virus type 1 (HIV-1) is disproportionately influenced by evolution in the five variable regions of the virus surface envelope glycoprotein (gp120). Insertions and deletions (indels) are a significant source of evolutionary change in these regions. However, the influx of indels relative to nucleotide substitutions has not yet been quantified through a comparative analysis of HIV-1 sequence data. Here we develop and report results from a phylogenetic method to estimate indel rates for the gp120 variable regions across five major subtypes and two circulating recombinant forms (CRFs) of HIV-1 group M. We processed over 26,000 published HIV-1 gp120 sequences, from which we extracted 6,605 sequences for phylogenetic analysis. In brief, our method employs maximum likelihood to reconstruct phylogenies scaled in time and fits a Poisson model to the observed distribution of indels between closely related pairs of sequences in the tree (cherries). The rate estimates ranged from 3.0e-5 to 1.5e-3 indels/nt/year and varied significantly among variable regions and subtypes. Indel rates were significantly lower in the region encoding variable loop V3, and also lower for HIV-1 subtype B relative to other subtypes. We also found that variable loops V1, V2 and V4 tended to accumulate significantly longer indels. Further, we observed that the nucleotide composition of indel sequences was significantly distinct from that of the flanking sequence in HIV-1 gp120. Indels affected potential N-linked glycosylation sites substantially more often in V1 and V2 than expected by chance, which is consistent with positive selection on glycosylation patterns within these regions of gp120. These results represent the first comprehensive measures of indel rates in HIV-1 gp120 across multiple subtypes and CRFs, and identifies novel and unexpected patterns for further research in the molecular evolution of HIV-1.

scholarly journals Increased HIV Subtype Diversity Reflecting Demographic Changes in the HIV Epidemic in New South Wales, Australia

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1402
Author(s):  
Francesca Di Giallonardo ◽  
Angie Pinto ◽  
Phillip Keen ◽  
Ansari Shaik ◽  
Alex Carrera ◽  
...  
Keyword(s):  
New South ◽  
New South Wales ◽  
Positive Association ◽  
Heterosexual Transmission ◽  
People Living With Hiv ◽  
Subtype C ◽  
Subtype B ◽  
South Wales ◽  
Hiv 1 ◽  
Over Time

Changes over time in HIV-1 subtype diversity within a population reflect changes in factors influencing the development of local epidemics. Here we report on the genetic diversity of 2364 reverse transcriptase sequences from people living with HIV-1 in New South Wales (NSW) notified between 2004 and 2018. These data represent >70% of all new HIV-1 notifications in the state over this period. Phylogenetic analysis was performed to identify subtype-specific transmission clusters. Subtype B and non-B infections differed across all demographics analysed (p < 0.001). We found a strong positive association for infections among females, individuals not born in Australia or reporting heterosexual transmission being of non-B origin. Further, we found an overall increase in non-B infections among men who have sex with men from 50 to 79% in the last 10 years. However, we also found differences between non-B subtypes; heterosexual transmission was positively associated with subtype C only. In addition, the majority of subtype B infections were associated with clusters, while the majority of non-B infections were singletons. However, we found seven non-B clusters (≥5 sequences) indicative of local ongoing transmission. In conclusion, we present how the HIV-1 epidemic has changed over time in NSW, becoming more heterogeneous with distinct subtype-specific demographic associations.

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