A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal

Müeller, Nancy; Das, Atze T.; Berkhout, Ben

doi:10.3390/v8070200

Cited by 8 publications

(6 citation statements)

References 54 publications

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“…Of these 11 positives, only one complete genome was recovered in EEC-3 (GeneBank MN055643). This sequence showed a G > A deleterious mutation in the major splice donor site in position 290 that suppose a very limited replicative capacity of the virus 30,31 . The remaining sequences (92%) showed important deletions throughout the genome mostly in pol to env genes.…”

Section: Sequence Analysis Genetic Variability and Evolutionary Dynamentioning

confidence: 99%

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Casado

Gálvez

Pernas

et al. 2020

Sci Rep

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Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/10 6 CD4 + t-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure. The use of combination antiretroviral therapy (ART) results in sustained undetectable plasma viremia in HIV-1-infected individuals. The success of ART led to initial optimism that HIV-1 may be cured by ART alone; however subsequent studies indicating that such a cure may take as long as 70 years 1,2 led researchers to attempt complementary strategies to reduce viral persistence and potentially facilitate HIV-1 remission 3. However, this has proven extremely difficult to achieve because it entails the eradication of any infectious viral form from the body. This has only putatively been achieved so far in two individuals, the Berlin and London patients 4,5. A less stringent objective, known as functional cure, consists in the permanent suppression of HIV-1 viral replication in the absence of ART even if full viral eradication is not achieved 6 .

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Section: Sequence Analysis Genetic Variability and Evolutionary Dynamentioning

confidence: 99%

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Casado

Gálvez

Pernas

et al. 2020

Sci Rep

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“…2010 ; Knoepfel and Berkhout 2011 ; Zanini and Neher 2013 ; Rollins et al. 2014 ; Mueller, Das, and Berkhout 2016 ) for studies focused specifically on various regions of the HIV-1 genome. The evolutionary signal derives from the dependence of evolutionary rates at individual sites on their degree of constraint in the secondary RNA structure ( Shapiro et al.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within and among infected hosts

et al. 2018

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Lentiviral RNA genomes contain structural elements that play critical roles in viral replication. Although structural features of 5′-untranslated regions have been well characterized, attempts to identify important structures in other genomic regions by Selective 2′-Hydroxyl Acylation analyzed by Primer Extension (SHAPE) have led to conflicting structural and mechanistic conclusions. Previous approaches accounted neither for sequence heterogeneity that is ubiquitous in viral populations, nor for selective constraints operating at the protein level. We developed an approach that augments SHAPE with phylogenetic analyses and applied it to investigate structure in coding regions (cRNA) within the HIV and SIV envelope genes. Analysis of single-genome SHAPE data with phylogenetic information from diverse lentiviral sequences argues against the conservation of a putative global gp120 RNA structure but points to the existence of core RNA sub-structures. Our findings establish a framework for considering sequence heterogeneity and protein function in de novo RNA structure inference approaches.

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“…The simulation of genetic data with both time-and spacedependent rates of migration and episodic selective sweeps could aid in distinguishing true from artefactual gene flow. While structured coalescent models incorporating variation in gene flow rates exist (67,68), sufficient statistical and computational power are needed to allow for variation across both space and time. Moreover, as these models are Bayesian in nature, prior probabilities describing a priori knowledge of migration rates involving each tissue is key.…”

Section: Discussionmentioning

confidence: 99%

Predator-Prey Dynamics of Intra-Host Simian Immunodeficiency Virus Evolution Within the Untreated Host

et al. 2021

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The dynamic nature of the SIV population during disease progression in the SIV/macaque model of AIDS and the factors responsible for its behavior have not been documented, largely owing to the lack of sufficient spatial and temporal sampling of both viral and host data from SIV-infected animals. In this study, we detail Bayesian coalescent inference of the changing collective intra-host viral effective population size (Ne) from various tissues over the course of infection and its relationship with what we demonstrate is a continuously changing immune cell repertoire within the blood. Although the relative contribution of these factors varied among hosts and time points, the adaptive immune response best explained the overall periodic dynamic behavior of the effective virus population. Data exposing the nature of the relationship between the virus and immune cell populations revealed the plausibility of an eco-evolutionary mathematical model, which was able to mimic the large-scale oscillations in Ne through virus escape from relatively few, early immunodominant responses, followed by slower escape from several subdominant and weakened immune populations. The results of this study suggest that SIV diversity within the untreated host is governed by a predator-prey relationship, wherein differing phases of infection are the result of adaptation in response to varying immune responses. Previous investigations into viral population dynamics using sequence data have focused on single estimates of the effective viral population size (Ne) or point estimates over sparse sampling data to provide insight into the precise impact of immune selection on virus adaptive behavior. Herein, we describe the use of the coalescent phylogenetic frame- work to estimate the relative changes in Ne over time in order to quantify the relationship with empirical data on the dynamic immune composition of the host. This relationship has allowed us to expand on earlier simulations to build a predator-prey model that explains the deterministic behavior of the virus over the course of disease progression. We show that sequential viral adaptation can occur in response to phases of varying immune pressure, providing a broader picture of the viral response throughout the entire course of progression to AIDS.

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A Phylogenetic Survey on the Structure of the HIV-1 Leader RNA Domain That Encodes the Splice Donor Signal

Cited by 8 publications

References 54 publications

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure

Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within and among infected hosts

Predator-Prey Dynamics of Intra-Host Simian Immunodeficiency Virus Evolution Within the Untreated Host

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