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.

scholarly journals Identification of a New HIV-1 BC Intersubtype Circulating Recombinant Form (CRF108_BC) in Spain

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 93
Author(s):  
Javier E. Cañada ◽  
Elena Delgado ◽  
Horacio Gil ◽  
Mónica Sánchez ◽  
Sonia Benito ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Basque Country ◽  
Recent Common Ancestor ◽  
Subtype C ◽  
Northern Spain ◽  
Most Recent Common Ancestor ◽  
Phylogenetic Cluster ◽  
Subtype B ◽  
Definition Of ◽  
Hiv 1

The extraordinary genetic variability of human immunodeficiency virus type 1 (HIV-1) group M has led to the identification of 10 subtypes, 102 circulating recombinant forms (CRFs) and numerous unique recombinant forms. Among CRFs, 11 derived from subtypes B and C have been identified in China, Brazil, and Italy. Here we identify a new HIV-1 CRF_BC in Northern Spain. Originally, a phylogenetic cluster of 15 viruses of subtype C in protease-reverse transcriptase was identified in an HIV-1 molecular surveillance study in Spain, most of them from individuals from the Basque Country and heterosexually transmitted. Analyses of near full-length genome sequences from six viruses from three cities revealed that they were BC recombinant with coincident mosaic structures different from known CRFs. This allowed the definition of a new HIV-1 CRF designated CRF108_BC, whose genome is predominantly of subtype C, with four short subtype B fragments. Phylogenetic analyses with database sequences supported a Brazilian ancestry of the parental subtype C strain. Coalescent Bayesian analyses estimated the most recent common ancestor of CRF108_BC in the city of Vitoria, Basque Country, around 2000. CRF108_BC is the first CRF_BC identified in Spain and the second in Europe, after CRF60_BC, both phylogenetically related to Brazilian subtype C strains.

scholarly journals Identification of CRF66_BF, a new HIV-1 circulating recombinant form of South American origin

2021 ◽  
Author(s):  
Joan Bacque ◽  
Elena Delgado ◽  
Sonia Benito ◽  
Maria Moreno-Lorenzo ◽  
Vanessa Montero ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Recent Common Ancestor ◽  
South American ◽  
Most Recent Common Ancestor ◽  
Phylogenetic Cluster ◽  
Subtype B ◽  
Sex With Men ◽  
Full Length Genome ◽  
South American Origin ◽  
Hiv 1

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 108 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n=4), Spain (n=3), Paraguay (n=1), Brazil (n=1), and Italy (n=1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17gag, integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF family clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF

scholarly journals Changes in impact of HLA class I allele expression on HIV-1 plasma virus loads at a population level over time

2010 ◽  
Vol 54 (4) ◽  
pp. 196-205 ◽  
Author(s):  
Michiko Koga ◽  
Ai Kawana-Tachikawa ◽  
David Heckerman ◽  
Takashi Odawara ◽  
Hitomi Nakamura ◽  
...  
Keyword(s):  
Population Level ◽  
Hla Class I ◽  
Class I ◽  
Plasma Virus ◽  
Allele Expression ◽  
Hiv 1 ◽  
Over Time

scholarly journals Identification of CRF66_BF, a New HIV-1 Circulating Recombinant Form of South American Origin

2021 ◽  
Vol 12 ◽  
Author(s):  
Joan Bacqué ◽  
Elena Delgado ◽  
Sonia Benito ◽  
María Moreno-Lorenzo ◽  
Vanessa Montero ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Recent Common Ancestor ◽  
South American ◽  
Most Recent Common Ancestor ◽  
Phylogenetic Cluster ◽  
Subtype B ◽  
Sex With Men ◽  
Full Length Genome ◽  
South American Origin ◽  
Hiv 1

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17gag, integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF “family” clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.

scholarly journals Nation-Wide Viral Sequence Analysis of HIV-1 Subtype B Epidemic in 2003–2012 Revealed a Contribution of Men Who Have Sex With Men to the Transmission Cluster Formation and Growth in Japan

2020 ◽  
Vol 2 ◽  
Author(s):  
Teiichiro Shiino ◽  
Atsuko Hachiya ◽  
Junko Hattori ◽  
Wataru Sugiura ◽  
Kazuhisa Yoshimura
Keyword(s):  
Recent Common Ancestor ◽  
Bayesian Posterior Probability ◽  
Newly Diagnosed ◽  
Surveillance Network ◽  
Relative Population ◽  
Most Recent Common Ancestor ◽  
Subtype B ◽  
Geographical Regions ◽  
Sex With Men ◽  
Hiv 1

Background: To better understand the epidemiology of human immunodeficiency virus type 1 (HIV-1) subtype B transmission in Japan, phylodynamic analysis of viral pol sequences was conducted on individuals newly diagnosed as HIV-1 seropositive.Methodology: A total of 5,018 patients newly diagnosed with HIV-1 infection and registered in the Japanese Drug Resistance HIV Surveillance Network from 2003 to 2012 were enrolled in the analysis. Using the protease-reverse transcriptase nucleotide sequences, their subtypes were determined, and phylogenetic relationships among subtype B sequences were inferred using three different methods: distance-matrix, maximum likelihood, and Bayesian Markov chain Monte Carlo. Domestically spread transmission clusters (dTCs) were identified based on the following criteria: >95% in interior branch test, >95% in Bayesian posterior probability and <10% in depth-first searches for sub-tree partitions. The association between dTC affiliation and individuals' demographics was analyzed using univariate and multivariate analyses.Results: Among the cases enrolled in the analysis, 4,398 (87.6%) were classified as subtype B. Many of them were Japanese men who had sex with men (MSM), and 3,708 (84.3%) belonged to any of 312 dTCs. Among these dTCs, 243 (77.9%) were small clusters with <10 individuals, and the largest cluster consisted of 256 individuals. Most dTCs had median time of the most recent common ancestor between 1995 and 2005, suggesting that subtype B infection was spread among MSMs in the second half of the 1990s. Interestingly, many dTCs occurred within geographical regions. Comparing with singleton cases, TCs included more MSM, young person, and individuals with high CD4+ T-cell count at the first consultation. Furthermore, dTC size was significantly correlated with gender, age, transmission risks, recent diagnosis and relative population size of the region mainly distributed.Conclusions: Our study clarified that major key population of HIV-1 subtype B epidemic in Japan is local MSM groups. The study suggests that HIV-1 subtype B spread via episodic introductions into the local MSM groups, some of the viruses spread to multiple regions. Many cases in dTC were diagnosed during the early phase of infection, suggesting their awareness to HIV risks.

scholarly journals Mutually Exclusive T-Cell Receptor Induction and Differential Susceptibility to Human Immunodeficiency Virus Type 1 Mutational Escape Associated with a Two-Amino-Acid Difference between HLA Class I Subtypes

2006 ◽  
Vol 81 (4) ◽  
pp. 1619-1631 ◽  
Author(s):  
Xu G. Yu ◽  
Mathias Lichterfeld ◽  
Senica Chetty ◽  
Katie L. Williams ◽  
Stanley K. Mui ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Viral Escape ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIPMF). When this epitope is presented by HLA-B*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HLA-B*5703 induces an entirely different, more heterogeneous TCR β-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703+ individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations.

scholarly journals Favorable and Unfavorable HLA Class I Alleles and Haplotypes in Zambians Predominantly Infected with Clade C Human Immunodeficiency Virus Type 1

2002 ◽  
Vol 76 (16) ◽  
pp. 8276-8284 ◽  
Author(s):  
Jianming Tang ◽  
Shenghui Tang ◽  
Elena Lobashevsky ◽  
Angela D. Myracle ◽  
Ulgen Fideli ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Hla Class I ◽  
Class I ◽  
Hla Class I Molecules ◽  
Immunodeficiency Virus ◽  
Clade C ◽  
Hiv 1

ABSTRACT The setpoint of viral RNA concentration (viral load [VL]) during chronic human immunodeficiency virus type 1 (HIV-1) infection reflects a virus-host equilibration closely related to CD8+ cytotoxic T-lymphocyte (CTL) responses, which rely heavily on antigen presentation by the human major histocompatibility complex (MHC) (i.e., HLA) class I molecules. Differences in HIV-1 VL among 259 mostly clade C virus-infected individuals (137 females and 122 males) in the Zambia-UAB HIV Research Project (ZUHRP) were associated with several HLA class I alleles and haplotypes. In particular, general linear model analyses revealed lower log10 VL among those with HLA allele B*57 (P = 0.002 [without correction]) previously implicated in favorable response and in those with HLA B*39 and A*30-Cw*03 (P = 0.002 to 0.016); the same analyses also demonstrated higher log10 VL among individuals with A*02-Cw*16, A*23-B*14, and A*23-Cw*07 (P = 0.010 to 0.033). These HLA effects remained strong (P = 0.0002 to 0.075) after adjustment for age, gender, and duration of infection and persisted across three orders of VL categories (P = 0.001 to 0.084). In contrast, neither B*35 (n = 15) nor B*53 (n = 53) showed a clear disadvantage such as that reported elsewhere for these closely related alleles. Other HLA associations with unusually high (A*68, B*41, B*45, and Cw*16) or low (B*13, Cw*12, and Cw*18) VL were either unstable or reflected their tight linkage respecting disequilibria with other class I variants. The three consistently favorable HLA class I variants retained in multivariable models and in alternative analyses were present in 30.9% of subjects with the lowest (<10,000 copies per ml) and 3.1% of those with the highest (>100,000) VL. Clear differential distribution of HLA profiles according to level of viremia suggests important host genetic contribution to the pattern of immune control and escape during HIV-1 infection.

Characteristics allelic of Human Leukocyte Antigen class I genotype and association with viral load and CD4 cell count in HIV-1 infected patients, Hanoi 2014 – 2016

2021 ◽  
Vol 31 (4) ◽  
pp. 43-50
Author(s):  
Tran Thi Minh Tam ◽  
Nguyen Thuy Linh ◽  
Phan Ha My ◽  
Nguyen Thi Lan Anh
Keyword(s):  
Viral Load ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Cd4 Cell Count ◽  
Leukocyte Antigen ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

Human Leukocyte Antigen (HLA) class I plays a regulatory role in cellular immune response to HIV-1 infection. The role of HLA alleles in HIV progression via viral load and CD4 cell count is well known. HLA class I is polymorphic and distributed differently by nation. This descriptive cross-sectional study was performed on 303 HIV-1 infected patients in 2014 - 2016, with aims to (i) characterize HLA class I genotype with 4-digit nomenclature and (ii) identify specifc alleles in correlate with CD4 cell counts and HIV viral load. 117 allele genotypes have been identifed, including 28 HLA-A alleles, 54 HLA-B alleles and 35 HLA-C alleles. The results showed that the most prevalent alleles in the population include A*11:01 (30.7%), B*15:02 (15.2%) and C*08:01 (17.1%). The frequency of haplotype created from these alleles is 8.4%. A*02:03, B*46:01 related to gender and ethnicity respectively. In conclusion, the study provided detailed pattern of HLA class I expression in a study population of HIV-1 infected patients and reported for the frst time the associated B*51:01, C*14:02 alleles associated to an increase in CD4 cell counts.

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