Convergent evolution as an indicator for selection during acute HIV-1 infection

AbstractConvergent evolution describes the process of different populations acquiring similar phenotypes or genotypes. Complex organisms with large genomes only rarely and only under very strong selection converge to the same genotype. In contrast, independent virus populations with very small genomes often acquire identical mutations. Here we test the hypothesis of whether convergence in early HIV-1 infection is common enough to serve as an indicator for selection. To this end, we measure the number of convergent mutations in a well-studied dataset of full-length HIV-1envgenes sampled from HIV-1 infected individuals during early infection. We compare this data to a neutral model and find an excess of convergent mutations. Convergent mutations are not evenly distributed across the env gene, but more likely to occur in gp41, which suggests that convergent mutations provide a selective advantage and hence are positively selected. In contrast, mutations that are only found in an HIV-1 population of a single individual are significantly affected by purifying selection. Our analysis suggests that comparisons between convergent and private mutations with neutral models allow us to identify positive and negative selection in small viral genomes. Our results also show that selection significantly shapes HIV-1 populations even before the onset of the adaptive immune system.

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Extending the Coding Potential of Viral Genomes with Overlapping Antisense ORFs: A Case for the De Novo Creation of the Gene Encoding the Antisense Protein ASP of HIV-1

Viruses ◽

10.3390/v14010146 ◽

2022 ◽

Vol 14 (1) ◽

pp. 146

Author(s):

Angelo Pavesi ◽

Fabio Romerio

Keyword(s):

De Novo ◽

Point Mutations ◽

Selective Advantage ◽

Genomic Region ◽

Fine Tuning ◽

Sequence Evolution ◽

Viral Genomes ◽

Stop Codons ◽

Hiv 1

Gene overprinting occurs when point mutations within a genomic region with an existing coding sequence create a new one in another reading frame. This process is quite frequent in viral genomes either to maximize the amount of information that they encode or in response to strong selective pressure. The most frequent scenario involves two different reading frames in the same DNA strand (sense overlap). Much less frequent are cases of overlapping genes that are encoded on opposite DNA strands (antisense overlap). One such example is the antisense ORF, asp in the minus strand of the HIV-1 genome overlapping the env gene. The asp gene is highly conserved in pandemic HIV-1 strains of group M, and it is absent in non-pandemic HIV-1 groups, HIV-2, and lentiviruses infecting non-human primates, suggesting that the ~190-amino acid protein that is expressed from this gene (ASP) may play a role in virus spread. While the function of ASP in the virus life cycle remains to be elucidated, mounting evidence from several research groups indicates that ASP is expressed in vivo. There are two alternative hypotheses that could be envisioned to explain the origin of the asp ORF. On one hand, asp may have originally been present in the ancestor of contemporary lentiviruses, and subsequently lost in all descendants except for most HIV-1 strains of group M due to selective advantage. Alternatively, the asp ORF may have originated very recently with the emergence of group M HIV-1 strains from SIVcpz. Here, we used a combination of computational and statistical approaches to study the genomic region of env in primate lentiviruses to shed light on the origin, structure, and sequence evolution of the asp ORF. The results emerging from our studies support the hypothesis of a recent de novo addition of the antisense ORF to the HIV-1 genome through a process that entailed progressive removal of existing internal stop codons from SIV strains to HIV-1 strains of group M, and fine tuning of the codon sequence in env that reduced the chances of new stop codons occurring in asp. Altogether, the study supports the notion that the HIV-1 asp gene encodes an accessory protein, providing a selective advantage to the virus.

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Convergent evolution as an indicator for selection during acute HIV-1 infection

10.24072/pcjournal.6 ◽

2021 ◽

Vol 1 ◽

pp. 1-None

Author(s):

Frederic Bertels ◽

Karin J. Metzner ◽

Roland Regoes

Keyword(s):

Convergent Evolution ◽

Acute Hiv ◽

Hiv 1

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OLGenie: Estimating Natural Selection to Predict Functional Overlapping Genes

Molecular Biology and Evolution ◽

10.1093/molbev/msaa087 ◽

2020 ◽

Cited By ~ 2

Author(s):

Chase W Nelson ◽

Zachary Ardern ◽

Xinzhu Wei

Keyword(s):

Natural Selection ◽

Protein Gene ◽

Purifying Selection ◽

Biological Sequences ◽

Overlapping Genes ◽

Protein Coding ◽

Discriminatory Ability ◽

Viral Genomes ◽

Scalable Methods ◽

Hiv 1

Abstract Purifying (negative) natural selection is a hallmark of functional biological sequences, and can be detected in protein-coding genes using the ratio of nonsynonymous to synonymous substitutions per site (dN/dS). However, when two genes overlap the same nucleotide sites in different frames, synonymous changes in one gene may be nonsynonymous in the other, perturbing dN/dS. Thus, scalable methods are needed to estimate functional constraint specifically for overlapping genes (OLGs). We propose OLGenie, which implements a modification of the Wei-Zhang method. Assessment with simulations and controls from viral genomes (58 OLGs and 176 non-OLGs) demonstrates low false positive rates and good discriminatory ability in differentiating true OLGs from non-OLGs. We also apply OLGenie to the unresolved case of HIV-1’s putative antisense protein gene, showing significant purifying selection. OLGenie can be used to study known OLGs and to predict new OLGs in genome annotation. Software and example data are freely available at https://github.com/chasewnelson/OLGenie.

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OLGenie: Estimating Natural Selection to Predict Functional Overlapping Genes

10.1101/2019.12.14.876607 ◽

2019 ◽

Cited By ~ 1

Author(s):

Chase W. Nelson ◽

Zachary Ardern ◽

Xinzhu Wei

Keyword(s):

Natural Selection ◽

Purifying Selection ◽

Biological Sequences ◽

Overlapping Genes ◽

Protein Coding ◽

Discriminatory Ability ◽

Viral Genomes ◽

Protein Coding Genes ◽

Scalable Methods ◽

Hiv 1

AbstractPurifying (negative) natural selection is a hallmark of functional biological sequences, and can be detected in protein-coding genes using the ratio of nonsynonymous to synonymous substitutions per site (dN/dS). However, when two genes overlap the same nucleotide sites in different frames, synonymous changes in one gene may be nonsynonymous in the other, perturbing dN/dS. Thus, scalable methods are needed to estimate functional constraint specifically for overlapping genes (OLGs). We propose OLGenie, which implements a modification of the Wei-Zhang method. Assessment with simulations and controls from viral genomes (58 OLGs and 176 non-OLGs) demonstrates low false positive rates and good discriminatory ability in differentiating true OLGs from non-OLGs. We also apply OLGenie to the unresolved case of HIV-1’s putative antisense protein gene, showing significant purifying selection. OLGenie can be used to study known OLGs and to predict new OLGs in genome annotation. Software and example data are freely available at https://github.com/chasewnelson/OLGenie.

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Faculty Opinions recommendation of Detection of low-level K65R variants in nucleoside reverse transcriptase inhibitor-naive chronic and acute HIV-1 subtype C infections.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.12019956.13157054 ◽

2011 ◽

Author(s):

Mark Wainberg ◽

Dimitrios Coutsinos

Keyword(s):

Reverse Transcriptase ◽

Nucleoside Reverse Transcriptase Inhibitor ◽

Transcriptase Inhibitor ◽

Subtype C ◽

Low Level ◽

Acute Hiv ◽

Reverse Transcriptase Inhibitor ◽

Hiv 1

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Faculty Opinions recommendation of Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14292.471794 ◽

2006 ◽

Author(s):

Ann Duerr

Keyword(s):

Viral Load ◽

High Risk ◽

Plasma Viral Load ◽

African Women ◽

Set Point ◽

Acute Hiv ◽

Hiv Type 1 ◽

Hiv 1

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PCIP-seq: simultaneous sequencing of integrated viral genomes and their insertion sites with long reads

Genome Biology ◽

10.1186/s13059-021-02307-0 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Maria Artesi ◽

Vincent Hahaut ◽

Basiel Cole ◽

Laurens Lambrechts ◽

Fereshteh Ashrafi ◽

...

Keyword(s):

Viral Genome ◽

Clonal Expansion ◽

Endogenous Retroviruses ◽

Viral Genomes ◽

Short Read Sequencing ◽

Long Reads ◽

Infected Cells ◽

Insertion Sites ◽

Viral Insertion ◽

Hiv 1

AbstractThe integration of a viral genome into the host genome has a major impact on the trajectory of the infected cell. Integration location and variation within the associated viral genome can influence both clonal expansion and persistence of infected cells. Methods based on short-read sequencing can identify viral insertion sites, but the sequence of the viral genomes within remains unobserved. We develop PCIP-seq, a method that leverages long reads to identify insertion sites and sequence their associated viral genome. We apply the technique to exogenous retroviruses HTLV-1, BLV, and HIV-1, endogenous retroviruses, and human papillomavirus.

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The antiviral factor APOBEC3G improves CTL recognition of cultured HIV-infected T cells

Journal of Experimental Medicine ◽

10.1084/jem.20091933 ◽

2009 ◽

Vol 207 (1) ◽

pp. 39-49 ◽

Cited By ~ 63

Author(s):

Nicoletta Casartelli ◽

Florence Guivel-Benhassine ◽

Romain Bouziat ◽

Samantha Brandler ◽

Olivier Schwartz ◽

...

Keyword(s):

Cytidine Deaminase ◽

Adaptive Immune System ◽

Antiviral Effect ◽

Inhibitory Effect ◽

Hiv Replication ◽

Viral Infectivity Factor ◽

Cellular Immune ◽

Vif Protein ◽

The Impact ◽

Hiv 1

The cytidine deaminase APOBEC3G (A3G) enzyme exerts an intrinsic anti–human immunodeficiency virus (HIV) defense by introducing lethal G-to-A hypermutations in the viral genome. The HIV-1 viral infectivity factor (Vif) protein triggers degradation of A3G and counteracts this antiviral effect. The impact of A3G on the adaptive cellular immune response has not been characterized. We examined whether A3G-edited defective viruses, which are known to express truncated or misfolded viral proteins, activate HIV-1–specific (HS) CD8+ cytotoxic T lymphocytes (CTLs). To this end, we compared the immunogenicity of cells infected with wild-type or Vif-deleted viruses in the presence or absence of the cytidine deaminase. The inhibitory effect of A3G on HIV replication was associated with a strong activation of cocultivated HS-CTLs. CTL activation was particularly marked with Vif-deleted HIV and with viruses harboring A3G. Enzymatically inactive A3G mutants failed to enhance CTL activation. We also engineered proviruses bearing premature stop codons in their genome as scars of A3G editing. These viruses were not infectious but potently activated HS-CTLs. Therefore, the pool of defective viruses generated by A3G represents an underestimated source of viral antigens. Our results reveal a novel function for A3G, acting not only as an intrinsic antiviral factor but also as an inducer of the adaptive immune system.

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