Faculty Opinions recommendation of HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

Abstract Phylogenetic studies have contributed to our understanding of the early epidemic onset of HIV-1 in the Democratic Republic of Congo (DRC); however, the factors driving its early emergence and establishment in human populations still remain unresolved. In order to determine the key aspects of its successful epidemic spread, complete genome data are required from samples representative of the viral diversity in the DRC. In this study, we have established a universal PCR-assay that uses seven different panels of primers to produce overlapping amplicons covering the complete HIV genome. To circumvent the limitations of purifying these fragments and sequencing them with traditional approaches, we have developed a massive parallel sequencing method and a protocol for efficiently assembling HIV-1 genomes. A total of thirty-six samples, collected between 1997 and 2001 from different locations across the DRC, have been obtained, and, at this stage, we are focusing on complementing our dataset with more archival samples that can be used as HIV ‘molecular fossils’. By generating complete genome phylogeographic data from the DRC, we aim to create a genomic window into the past evolutionary and epidemiological dynamics of HIV-1 in Central Africa and understand the natural history of this devastating pandemic.

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Patterns of Human Immunodeficiency Virus Type 1 Recombination Ex Vivo Provide Evidence for Coadaptation of Distant Sites, Resulting in Purifying Selection for Intersubtype Recombinants during Replication

Journal of Virology ◽

10.1128/jvi.00276-10 ◽

2010 ◽

Vol 84 (15) ◽

pp. 7651-7661 ◽

Cited By ~ 28

Author(s):

Andrea Galli ◽

Mary Kearney ◽

Olga A. Nikolaitchik ◽

Sloane Yu ◽

Mario P. S. Chin ◽

...

Keyword(s):

Ex Vivo ◽

Purifying Selection ◽

Human Populations ◽

Major Barrier ◽

Subtype B ◽

Single Genome ◽

Immunodeficiency Virus ◽

Multiple Cycle ◽

Hiv 1

ABSTRACT High-frequency recombination is a hallmark of HIV-1 replication. Recombination can occur between two members of the same subtype or between viruses from two different subtypes, generating intra- or intersubtype recombinants, respectively. Many intersubtype recombinants have been shown to circulate in human populations. We hypothesize that sequence diversity affects the emergence of viable recombinants by decreasing recombination events and reducing the ability of the recombinants to replicate. To test our hypothesis, we compared recombination between two viruses containing subtype B pol genes (B/B) and between viruses with pol genes from subtype B or F (B/F). Recombination events generated during a single cycle of infection without selection pressure on pol gene function were analyzed by single-genome sequencing. We found that recombination occurred slightly (∼30%) less frequently in B/F than in B/B viruses, and the overall distribution of crossover junctions in pol was similar for the two classes of recombinants. We then examined the emergence of recombinants in a multiple cycle assay, so that functional pol gene products were selected. We found that the emerging B/B recombinants had complex patterns, and the crossover junctions were distributed throughout the pol gene. In contrast, selected B/F recombinants had limited recombination patterns and restricted crossover junction distribution. These results provide evidence for the evolved coadapted sites in variants from different subtypes; these sites may be segregated by recombination events, causing the newly generated intersubtype recombinants to undergo purifying selection. Therefore, the ability of the recombinants to replicate is the major barrier for many of these viruses.

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The subtypes of human immunodeficiency virus in Australia and Asia

Sexual Health ◽

10.1071/sh03002 ◽

2004 ◽

Vol 1 (1) ◽

pp. 1 ◽

Cited By ~ 6

Author(s):

Robert Oelrichs

Keyword(s):

Human Immunodeficiency Virus ◽

Genetic Variability ◽

Distribution Patterns ◽

Human Populations ◽

Regional Diversity ◽

Subtype B ◽

Immunodeficiency Virus ◽

Australasian Region ◽

Hiv 1

Worldwide, the human immunodeficiency virus exhibits a great genetic variability, with multiple circulating subtypes of the virus. This variability allows study of the movement of HIV strains within and between human populations but also has implications for diagnosis, treatment and monitoring. The type of HIV causing the epidemic in Australia is changing from being homogeneous subtype B, reflecting a greater regional diversity. In this paper the classification of HIV-1 subtypes and their distribution within the Australasian region are reviewed and the implications of these distribution patterns discussed.

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Revealing the history of infectious disease epidemics through phylogenetic trees

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1995.0088 ◽

1995 ◽

Vol 349 (1327) ◽

pp. 33-40 ◽

Cited By ~ 54

Keyword(s):

Phylogenetic Trees ◽

Viral Transmission ◽

Human Populations ◽

Viral Sequence ◽

Immunodeficiency Virus ◽

History Of ◽

The Difference ◽

Disease Epidemics ◽

Hiv 1

Phylogenetic trees play an increasing role in molecular epidemiology, where they have been used to understand the forces that shape patterns of viral sequence diversity. Phylogenetic trees can also be used to trace the dynamics of viral transmission within populations. Case studies document the worldwide spread of Human Immunodeficiency Virus type 1 (HIV -1) and hepatitis C virus (HCV). Despite similarities between these viruses, especially in their transmission routes, they are shown to have very different epidemiological histories. A possible reason for the difference is that HCV has coexisted longer with human populations.

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Large Evolutionary Rate Heterogeneity among and within HIV-1 Subtypes and CRFs

Viruses ◽

10.3390/v13091689 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1689

Author(s):

Arshan Nasir ◽

Mira Dimitrijevic ◽

Ethan Romero-Severson ◽

Thomas Leitner

Keyword(s):

Evolutionary Rate ◽

Virus Genome ◽

Rate Variation ◽

Human Populations ◽

Host Immune System ◽

Virus Spread ◽

Rate Heterogeneity ◽

Hiv 1 ◽

Subtype 3 ◽

Diverse Virus

HIV-1 is a fast-evolving, genetically diverse virus presently classified into several groups and subtypes. The virus evolves rapidly because of an error-prone polymerase, high rates of recombination, and selection in response to the host immune system and clinical management of the infection. The rate of evolution is also influenced by the rate of virus spread in a population and nature of the outbreak, among other factors. HIV-1 evolution is thus driven by a range of complex genetic, social, and epidemiological factors that complicates disease management and prevention. Here, we quantify the evolutionary (substitution) rate heterogeneity among major HIV-1 subtypes and recombinants by analyzing the largest collection of HIV-1 genetic data spanning the widest possible geographical (100 countries) and temporal (1981–2019) spread. We show that HIV-1 substitution rates vary substantially, sometimes by several folds, both across the virus genome and between major subtypes and recombinants, but also within a subtype. Across subtypes, rates ranged 3.5-fold from 1.34 × 10−3 to 4.72 × 10−3 in env and 2.3-fold from 0.95 × 10−3 to 2.18 × 10−3 substitutions site−1 year−1 in pol. Within the subtype, 3-fold rate variation was observed in env in different human populations. It is possible that HIV-1 lineages in different parts of the world are operating under different selection pressures leading to substantial rate heterogeneity within and between subtypes. We further highlight how such rate heterogeneity can complicate HIV-1 phylodynamic studies, specifically, inferences on epidemiological linkage of transmission clusters based on genetic distance or phylogenetic data, and can mislead estimates about the timing of HIV-1 lineages.

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Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

SciVee ◽

10.4016/2755.01 ◽

2007 ◽

Author(s):

Art Poon ◽

Sergei Pond ◽

Phil Bennett ◽

Douglas Richman ◽

Andrew Brown ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Human Populations ◽

Hiv 1

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Multiple nonfunctional alleles of CCR5 are frequent in various human populations

Blood ◽

10.1182/blood.v96.5.1638.h8001638_1638_1645 ◽

2000 ◽

Vol 96 (5) ◽

pp. 1638-1645 ◽

Cited By ~ 1

Author(s):

Cédric Blanpain ◽

Benhur Lee ◽

Marie Tackoen ◽

Bridget Puffer ◽

Alain Boom ◽

...

Keyword(s):

Cell Surface ◽

Receptor Activation ◽

Human Populations ◽

Type I ◽

Binding Affinities ◽

Functional Responses ◽

Functional Consequences ◽

Relative Inability ◽

Specific Alteration ◽

Hiv 1

CCR5 is the major coreceptor for macrophage-tropic strains of the human immunodeficiency virus type I (HIV-1). Homozygotes for a 32-base pair (bp) deletion in the coding sequence of the receptor (CCR5Δ32) were found to be highly resistant to viral infection, and CCR5 became, therefore, one of the paradigms illustrating the influence of genetic variability onto individual susceptibility to infectious and other diseases. We investigated the functional consequences of 16 other natural CCR5 mutations described in various human populations. We found that 10 of these variants are efficiently expressed at the cell surface, bind [125I]-MIP-1β with affinities similar to wtCCR5, respond functionally to chemokines, and act as HIV-1 coreceptors. In addition to Δ32, six mutations were characterized by major alterations in their functional response to chemokines, as a consequence of intracellular trapping and poor expression at the cell surface (C101X, FS299), general or specific alteration of ligand binding affinities (C20S, C178R, A29S), or relative inability to mediate receptor activation (L55Q). A29S displayed an unusual pharmacological profile, binding and responding to MCP-2 similarly to wtCCR5, but exhibiting severely impaired binding and functional responses to MIP-1α, MIP-1β, and RANTES. In addition to Δ32, only C101X was totally unable to mediate entry of HIV-1. The fact that nonfunctional CCR5 alleles are relatively frequent in various human populations reinforces the hypothesis of a selective pressure favoring these alleles.

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