scholarly journals CD4 receptor diversity represents an ancient protection mechanism against primate lentiviruses

2021 ◽  
Vol 118 (13) ◽  
pp. e2025914118
Author(s):  
Ronnie M. Russell ◽  
Frederic Bibollet-Ruche ◽  
Weimin Liu ◽  
Scott Sherrill-Mix ◽  
Yingying Li ◽  
...  

Infection with human and simian immunodeficiency viruses (HIV/SIV) requires binding of the viral envelope glycoprotein (Env) to the host protein CD4 on the surface of immune cells. Although invariant in humans, the Env binding domain of the chimpanzee CD4 is highly polymorphic, with nine coding variants circulating in wild populations. Here, we show that within-species CD4 diversity is not unique to chimpanzees but found in many African primate species. Characterizing the outermost (D1) domain of the CD4 protein in over 500 monkeys and apes, we found polymorphic residues in 24 of 29 primate species, with as many as 11 different coding variants identified within a single species. D1 domain amino acid replacements affected SIV Env-mediated cell entry in a single-round infection assay, restricting infection in a strain- and allele-specific fashion. Several identical CD4 polymorphisms, including the addition of N-linked glycosylation sites, were found in primate species from different genera, providing striking examples of parallel evolution. Moreover, seven different guenons (Cercopithecus spp.) shared multiple distinct D1 domain variants, pointing to long-term trans-specific polymorphism. These data indicate that the HIV/SIV Env binding region of the primate CD4 protein is highly variable, both within and between species, and suggest that this diversity has been maintained by balancing selection for millions of years, at least in part to confer protection against primate lentiviruses. Although long-term SIV-infected species have evolved specific mechanisms to avoid disease progression, primate lentiviruses are intrinsically pathogenic and have left their mark on the host genome.

Elements ◽  
2015 ◽  
Vol 11 (2) ◽  
Author(s):  
Allyson Tank

Restriction factors are implemented in long-term evolutionary "arms races," in which viral antagonists drive the evolution of host proteins, and vice versa. Consequently, restriction factors are remarkably variable, displaying polymorphism within species and divergence between species as a result of positive selection. This paper investigates diversity in the APOBEC3F (A3F) restriction factors of Old World primates in order to determine whether they display evidence of involvement in an evolutionary "arms race." We speculated that genetic variability in A3F could reflect evolutionary conflict with the VIF proteins of primate lentiviruses, which are known to enhance viral replication by binding and degrading host A3 proteins. A3Fs of several Old World primate species were genotyped, and the sequences revealed both intra-spcies diversity and inter-species divergence. Representative rhesus macaque (<em>macaca mulatta</em>) sequences were cloned and tested for sensitivity to VIFs from various simin immunodeficiency viruses (SIVs). Evolution of A3F in the rhesus lineage is not due to selection by SIVs, but may reflect antagonism by another retrovirus.


2018 ◽  
Author(s):  
Xiaoheng Cheng ◽  
Michael DeGiorgio

AbstractTrans-species polymorphism has been widely used as a key sign of long-term balancing selection across multiple species. However, such sites are often rare in the genome, and could result from mutational processes or technical artifacts. Few methods are yet available to specifically detect footprints of trans-species balancing selection without using trans-species polymorphic sites. In this study, we develop summary- and model-based approaches that are each specifically tailored to uncover regions of long-term balancing selection shared by a set of species by using genomic patterns of intra-specific polymorphism and inter-specific fixed differences. We demonstrate that our trans-species statistics have substantially higher power than single-species approaches to detect footprints of trans-species balancing selection, and are robust to those that do not affect all tested species. We further apply our model-based methods to human and chimpanzee whole genome sequencing data. In addition to the previously-established MHC and malaria resistance-associated FREM3/GYPE regions, we also find outstanding genomic regions involved in barrier integrity and innate immunity, such as the GRIK1/CLDN17 intergenic region, and the SLC35F1 and ABCA13 genes. Our findings not only echo the significance of pathogen defense, but also reveal novel candidates in maintaining balanced polymorphisms across human and chimpanzee lineages. Finally, we show that these trans-species statistics can be applied to and work well for an arbitrary number of species, and integrate them into open-source software packages for ease of use by the scientific community.


Author(s):  
Jesús F. Águila ◽  
Vanessa Montoya ◽  
Javier Samper ◽  
Luis Montenegro ◽  
Georg Kosakowski ◽  
...  

AbstractSophisticated modeling of the migration of sorbing radionuclides in compacted claystones is needed for supporting the safety analysis of deep geological repositories for radioactive waste, which requires robust modeling tools/codes. Here, a benchmark related to a long term laboratory scale diffusion experiment of cesium, a moderately sorbing radionuclide, through Opalinus clay is presented. The benchmark was performed with the following codes: CORE2DV5, Flotran, COMSOL Multiphysics, OpenGeoSys-GEM, MCOTAC and PHREEQC v.3. The migration setup was solved with two different conceptual models, i) a single-species model by using a look-up table for a cesium sorption isotherm and ii) a multi-species diffusion model including a complex mechanistic cesium sorption model. The calculations were performed for three different cesium boundary concentrations (10−3, 10−5, 10−7 mol / L) to investigate the models/codes capabilities taking into account the nonlinear sorption behavior of cesium. Generally, good agreement for both single- and multi-species benchmark concepts could be achieved, however, some discrepancies have been identified, especially near the boundaries, where code specific spatial (and time) discretization had to be improved to achieve better agreement at the expense of longer computation times. In addition, the benchmark exercise yielded useful information on code performance, setup options, input and output data management, and post processing options. Finally, the comparison of single-species and multi-species model concepts showed that the single-species approach yielded generally earlier breakthrough, because this approach accounts neither for cation exchange of Cs+ with K+ and Na+, nor K+ and Na+ diffusion in the pore water.


Author(s):  
Haiming Tang ◽  
Chao Li ◽  
Lihong Shi ◽  
Li Wen ◽  
Kaikai Cheng ◽  
...  

Abstract Soil organic matter (SOM) and its fractions play an important role in maintaining or improving soil quality and soil fertility. Therefore, the effects of a 34-year long-term fertilizer regime on six functional SOM fractions under a double-cropping rice paddy field of southern China were studied in the current paper. The field experiment included four different fertilizer treatments: chemical fertilizer alone (MF), rice straw residue and chemical fertilizer (RF), 30% organic manure and 70% chemical fertilizer (OM) and without fertilizer input as control (CK). The results showed that coarse unprotected particulate organic matter (cPOM), biochemically, physically–biochemically and chemically protected silt-sized fractions (NH-dSilt, NH-μSilt and H-dSilt) were the main carbon (C) storage fractions under long-term fertilization conditions, accounting for 16.7–26.5, 31.1–35.6, 16.2–17.3 and 7.5–8.2% of the total soil organic carbon (SOC) content in paddy soil, respectively. Compared with control, OM treatment increased the SOC content in the cPOM, fine unprotected POM fraction, pure physically protected fraction and physico-chemically protected fractions by 58.9, 106.7, 117.6 and 28.3%, respectively. The largest proportion of SOC to total SOC in the different fractions was biochemically protected, followed by chemically and unprotected, and physically protected were the smallest. These results suggested that a physical protection mechanism plays an important role in stabilizing C of paddy soil. In summary, the results showed that higher functional SOM fractions and physical protection mechanism play an important role in SOM cycling in terms of C sequestration under the double-cropping rice paddy field.


1988 ◽  
Vol 98 (11) ◽  
pp. 1183???1189 ◽  
Author(s):  
Johannes G. Swart ◽  
Harold F. Schuknecht

2010 ◽  
Vol 84 (7) ◽  
pp. 3576-3585 ◽  
Author(s):  
Marit J. van Gils ◽  
Evelien M. Bunnik ◽  
Judith A. Burger ◽  
Yodit Jacob ◽  
Becky Schweighardt ◽  
...  

ABSTRACT A substantial proportion of human immunodeficiency virus type 1 (HIV-1)-infected individuals has cross-reactive neutralizing activity in serum, with a similar prevalence in progressors and long-term nonprogressors (LTNP). We studied whether disease progression in the face of cross-reactive neutralizing serum activity is due to fading neutralizing humoral immunity over time or to viral escape. In three LTNP and three progressors, high-titer cross-reactive HIV-1-specific neutralizing activity in serum against a multiclade pseudovirus panel was preserved during the entire clinical course of infection, even after AIDS diagnosis in progressors. However, while early HIV-1 variants from all six individuals could be neutralized by autologous serum, the autologous neutralizing activity declined during chronic infection. This could be attributed to viral escape and the apparent inability of the host to elicit neutralizing antibodies to the newly emerging viral escape variants. Escape from autologous neutralizing activity was not associated with a reduction in the viral replication rate in vitro. Escape from autologous serum with cross-reactive neutralizing activity coincided with an increase in the length of the variable loops and in the number of potential N-linked glycosylation sites in the viral envelope. Positive selection pressure was observed in the variable regions in envelope, suggesting that, at least in these individuals, these regions are targeted by humoral immunity with cross-reactive potential. Our results may imply that the ability of HIV-1 to rapidly escape cross-reactive autologous neutralizing antibody responses without the loss of viral fitness is the underlying explanation for the absent effect of potent cross-reactive neutralizing humoral immunity on the clinical course of infection.


2016 ◽  
Vol 33 (6) ◽  
pp. 1435-1447 ◽  
Author(s):  
Cesare de Filippo ◽  
Felix M. Key ◽  
Silvia Ghirotto ◽  
Andrea Benazzo ◽  
Juan R. Meneu ◽  
...  

2013 ◽  
Vol 71 (3) ◽  
pp. 681-688 ◽  
Author(s):  
Cynthia M. Jones

Abstract The importance of estuarine seagrass beds as nurseries for juvenile fish has become a universal paradigm, especially for estuaries that are as important as the Chesapeake Bay. Yet, scientific tests of this hypothesis were equivocal depending on species, location, and metrics. Moreover, seagrasses themselves are under threat and one-third of seagrasses have disappeared worldwide with 65% of their losses occurring in estuaries. Although there have been extensive studies of seagrasses in the Chesapeake Bay, surprisingly few studies have quantified the relationship between seagrass as nurseries for finfish in the Bay. Of the few studies that have directly evaluated the use of seagrass nurseries, most have concentrated on single species or were of short duration. Few landscape-level or long-term studies have examined this relationship in the Bay or explored the potential effect of climate change. This review paper summarizes the seagrass habitat value as nurseries and presents recent juvenile fish studies that address the dearth of research at the long term and landscape level with an emphasis on the Chesapeake Bay. An important conclusion upon the review of these studies is that predicting the effects of climate change on fishery production remains uncertain.


2021 ◽  
Author(s):  
Emma Berdan ◽  
Alexandre Blanckaert ◽  
Roger K Butlin ◽  
Thomas Flatt ◽  
Tanja Slotte ◽  
...  

Supergenes offer some of the most spectacular examples of long-term balancing selection in nature but their origin and maintenance remain a mystery. A critical aspect of supergenes is reduced recombination between arrangements. Reduced recombination protects adaptive multi-trait phenotypes, but can also lead to degeneration through mutation accumulation. Mutation accumulation can stabilize the system through the emergence of associative overdominance (AOD), destabilize the system, or lead to new evolutionary outcomes. One such outcome is the formation of balanced lethal systems, a maladaptive system where both supergene arrangements have accumulated deleterious mutations to the extent that both homozygotes are inviable, leaving only heterozygotes to reproduce. Here, we perform a simulation study to understand the conditions under which these different outcomes occur, assuming a scenario of introgression after allopatric divergence. We found that AOD aids the invasion of a new supergene arrangement and the establishment of a polymorphism. However, this polymorphism is easily destabilized by further mutation accumulation. While degradation may strengthen AOD, thereby stabilizing the supergene polymorphism, it is often asymmetric, which is the key disrupter of the quasi-equilibrium state of the polymorphism. Furthermore, mechanisms that accelerate degeneration also tend to amplify asymmetric mutation accumulation between the supergene arrangements and vice versa. As the evolution of a balanced lethal system requires symmetric degradation of both arrangements, this leaves highly restricted conditions under which such a system could evolve. We show that small population size and low dominance coefficients are critical factors, as these reduce the efficacy of selection. The dichotomy between the persistence of a polymorphism and degradation of supergene arrangements likely underlies the rarity of balanced lethal systems in nature.


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