AUTO-TUNE: selecting the distance threshold for inferring HIV transmission clusters.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret.

AUTO-TUNE: SELECTING THE DISTANCE THRESHOLD FOR INFERRING HIV TRANSMISSION CLUSTERS.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret.

High-Level Drug-Resistant Mutations among HIV-1 Subtype A6 and CRF02_AG in Kazakhstan.

HIV incidence in Kazakhstan increased by 73% between 2010 and 2020, with an estimated 35,000 people living with HIV (PLHIV) in 2020. The development of antiretroviral drug resistance is a major threat to effective antiretroviral therapy (ART), yet studies on the prevalence of drug resistance in Kazakhstan are sparse. In this study on the molecular epidemiology of HIV in Kazakhstan, we analyzed 968 partial HIV-1 sequences that were collected between 2017 and 2020 from PLHIV across all regions of Kazakhstan, covering almost 3% of PLHIV in 2020.

A large population sample of African HIV genomes from the 1980s reveals a reduction in subtype D over time associated with propensity for CXCR4 tropism.

We present 109 near full-length HIV genomes amplified from blood serum samples obtained during early 1986 from across Uganda, which to our knowledge is the earliest and largest population sample from the initial phase of the HIV epidemic in Africa. Consensus sequences were made from paired-end Illumina reads with a target-capture approach to amplify HIV material following poor success with standard approaches. In comparisons with a smaller 'intermediate' genome dataset from 1998 to 1999 and a 'modern' genome dataset from 2007 to 2016, the proportion of subtype D was significantly higher initially, dropping from 67% (73/109), to 57% (26/46) to 17% (82/465) respectively (p < 0.

Detection of HIV-1 Transmission Clusters from Dried Blood Spots within a Universal Test-and-Treat Trial in East Africa.

The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 and 488 HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections.

Employing phylogenetic tree shape statistics to resolve the underlying host population structure.

Background: Host population structure is a key determinant of pathogen and infectious disease transmission patterns. Pathogen phylogenetic trees are useful tools to reveal the population structure underlying an epidemic. Determining whether a population is structured or not is useful in informing the type of phylogenetic methods to be used in a given study.

Pervasive and non-random recombination in near full-length HIV genomes from Uganda.

Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome.

Non-disclosed men who have sex with men in UK HIV transmission networks: phylogenetic analysis of surveillance data.

Background: Patients who do not disclose their sexuality, including men who do not disclose same-sex behaviour, are difficult to characterise through traditional epidemiological approaches such as interviews. Using a recently developed method to detect large networks of viral sequences from time-resolved trees, we localised non-disclosed men who have sex with men (MSM) in UK transmission networks, gaining crucial insight into the behaviour of this group.

Methods: For this phylogenetic analysis, we obtained HIV pol sequences from the UK HIV Drug Resistance Database (UKRDB), a central repository for resistance tests done as part of routine clinical care throughout the UK.

Recent and Rapid Transmission of HIV Among People Who Inject Drugs in Scotland Revealed Through Phylogenetic Analysis.

Background: Harm reduction has dramatically reduced HIV incidence among people who inject drugs (PWID). In Glasgow, Scotland, <10 infections/year have been diagnosed among PWID since the mid-1990s. However, in 2015 a sharp rise in diagnoses was noted among PWID; many were subtype C with 2 identical drug-resistant mutations and some displayed low avidity, suggesting the infections were linked and recent.

HIV-TRACE (TRAnsmission Cluster Engine): a Tool for Large Scale Molecular Epidemiology of HIV-1 and Other Rapidly Evolving Pathogens.

In modern applications of molecular epidemiology, genetic sequence data are routinely used to identify clusters of transmission in rapidly evolving pathogens, most notably HIV-1. Traditional 'shoe-leather' epidemiology infers transmission clusters by tracing chains of partners sharing epidemiological connections (e.g.

A high HIV-1 strain variability in London, UK, revealed by full-genome analysis: Results from the ICONIC project.

Background & Methods: The ICONIC project has developed an automated high-throughput pipeline to generate HIV nearly full-length genomes (NFLG, i.e. from gag to nef) from next-generation sequencing (NGS) data.

Quantifying predictors for the spatial diffusion of avian influenza virus in China.

Background: Avian influenza virus (AIV) causes both severe outbreaks and endemic disease among poultry and has caused sporadic human infections in Asia, furthermore the routes of transmission in avian species between geographic regions can be numerous and complex. Using nucleotide sequences from the internal protein coding segments of AIV, we performed a Bayesian phylogeographic study to uncover regional routes of transmission and factors predictive of the rate of viral diffusion within China.

Results: We found that the Central area and Pan-Pearl River Delta were the two main sources of AIV diffusion, while the East Coast areas especially the Yangtze River delta, were the major targets of viral invasion.

Phylogenetic Tools for Generalized HIV-1 Epidemics: Findings from the PANGEA-HIV Methods Comparison.

Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa.

Using nearly full-genome HIV sequence data improves phylogeny reconstruction in a simulated epidemic.

HIV molecular epidemiology studies analyse viral pol gene sequences due to their availability, but whole genome sequencing allows to use other genes. We aimed to determine what gene(s) provide(s) the best approximation to the real phylogeny by analysing a simulated epidemic (created as part of the PANGEA_HIV project) with a known transmission tree. We sub-sampled a simulated dataset of 4662 sequences into different combinations of genes (gag-pol-env, gag-pol, gag, pol, env and partial pol) and sampling depths (100%, 60%, 20% and 5%), generating 100 replicates for each case.

A Direct Comparison of Two Densely Sampled HIV Epidemics: The UK and Switzerland.

Phylogenetic clustering approaches can elucidate HIV transmission dynamics. Comparisons across countries are essential for evaluating public health policies. Here, we used a standardised approach to compare the UK HIV Drug Resistance Database and the Swiss HIV Cohort Study while maintaining data-protection requirements.

Reconstructing the HIV-1 CRF02_AG and CRF06_cpx epidemics in Burkina Faso and West Africa using early samples.

Background: HIV-1 circulating recombinant forms (CRFs) represent viral recombinant lineages that play a significant role in the global epidemic. Two of them dominate the epidemic in Burkina Faso: CRF06_cpx (first described in this country) and CRF02_AG. We reconstructed the phylodynamics of both recombinant viruses in Burkina Faso and throughout West Africa.

Transmission of Non-B HIV Subtypes in the United Kingdom Is Increasingly Driven by Large Non-Heterosexual Transmission Clusters.

Background: The United Kingdom human immunodeficiency virus (HIV) epidemic was historically dominated by HIV subtype B transmission among men who have sex with men (MSM). Now 50% of diagnoses and prevalent infections are among heterosexual individuals and mainly involve non-B subtypes. Between 2002 and 2010, the prevalence of non-B diagnoses among MSM increased from 5.

Analysis of the history and spread of HIV-1 in Uganda using phylodynamics.

HIV prevalence has decreased in Uganda since the 1990s, but remains substantial within high-risk groups. Here, we reconstruct the history and spread of HIV subtypes A1 and D in Uganda and explore the transmission dynamics in high-risk populations. We analysed HIV pol sequences from female sex workers in Kampala (n = 42), Lake Victoria fisher-folk (n = 46) and a rural clinical cohort (n = 74), together with publicly available sequences from adjacent regions in Uganda (n = 412) and newly generated sequences from samples taken in Kampala in 1986 (n = 12).

Determining the phylogenetic and phylogeographic origin of highly pathogenic avian influenza (H7N3) in Mexico.

Highly pathogenic (HP) avian influenza virus (AIV) H7N3 outbreaks occurred 3 times in the Americas in the past 10 years and caused severe economic loss in the affected regions. In June/July 2012, new HP H7N3 outbreaks occurred at commercial farms in Jalisco, Mexico. Outbreaks continued to be identified in neighbouring states in Mexico till August 2013.

Phylogenetic analyses reveal HIV-1 infections between men misclassified as heterosexual transmissions.

Objective: HIV-1 subtype B infections are associated with MSM in the UK. Yet, around 13% of subtype B infections are found in those reporting heterosexual contact as transmission route. Using phylogenetics, we explored possible misclassification of sexual exposure among men diagnosed with HIV in the UK.

Intercontinental dispersal of HIV-1 subtype B associated with transmission among men who have sex with men in Japan.

Unlabelled: Transmission clusters of HIV-1 subtype B uniquely associated with the epidemic among men who have sex with men (MSM) in East Asia have recently been identified. Using the Los Alamos HIV sequence database and the UK HIV drug resistance database, we explored possible links between HIV MSM epidemics in East Asia and the rest of the world by using phylogenetic and molecular clock analyses. We found that JP.

The contribution of viral genotype to plasma viral set-point in HIV infection.

Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set.

Dynamics of the emergence and establishment of a newly dominant genotype of Japanese encephalitis virus throughout Asia.

Unlabelled: In recent years, genotype I (GI) of Japanese encephalitis virus (JEV) has displaced genotype III (GIII) as the dominant virus genotype throughout Asia. In this study, the largest collection of GIII and GI envelope gene-derived viral sequences assembled to date was used to reconstruct the spatiotemporal chronology of genotype displacement throughout Asia and to determine the evolutionary and epidemiological dynamics underlying this significant event. GI consists of two clades, GI-a and GI-b, with the latter being associated with displacement of GIII as the dominant JEV genotype throughout Asia in the 1990s.

Reassortment patterns of avian influenza virus internal segments among different subtypes.

Background: The segmented RNA genome of avian Influenza viruses (AIV) allows genetic reassortment between co-infecting viruses, providing an evolutionary pathway to generate genetic innovation. The genetic diversity (16 haemagglutinin and 9 neuraminidase subtypes) of AIV indicates an extensive reservoir of influenza viruses exists in bird populations, but how frequently subtypes reassort with each other is still unknown. Here we quantify the reassortment patterns among subtypes in the Eurasian avian viral pool by reconstructing the ancestral states of the subtypes as discrete states on time-scaled phylogenies with respect to the internal protein coding segments.

Novel HIV-1 recombinants spreading across multiple risk groups in the United Kingdom: the identification and phylogeography of Circulating Recombinant Form (CRF) 50_A1D.

Background: An increase in non-B HIV-1 infections among men who have sex with men (MSM) in the United Kingdom (UK) has created opportunities for novel recombinants to arise and become established. We used molecular mapping to characterize the importance of such recombinants to the UK HIV epidemic, in order to gain insights into transmission dynamics that can inform control strategies.

Methods And Results: A total of 55,556 pol (reverse transcriptase and protease) sequences in the UK HIV Drug Resistance Database were analyzed using Subtype Classification Using Evolutionary Algorithms (SCUEAL).