Morphological description of the midgut tract and midgut-hindgut junction in the larvae of the spider crab Maja brachydactyla Balss, 1922 (Malacostraca: Decapoda).

The midgut tract of decapods is a digestive organ involved in the synthesis of peritrophic membrane, food transport, absorption of nutrients, and osmoregulation. The midgut tract has been described in detail in adult decapods, but little information is available regarding the morphology and ultrastructure of the midgut tract in larval stages. The present study describes the midgut tract and the midgut-hindgut junction of the larvae of the common spider crab Maja brachydactyla Balss, 1922 using techniques that included dissection, light microscopy, and electron microscopy. The study is mainly focused on the stages of zoea I and megalopa. The results obtained in this study show that the larval midgut tract is a short and simple tube positioned anteriorly, between the stomach and the hindgut tract. During larval development, the maximum length of the midgut tract increases significantly, but no differences were found on either the maximum diameter or the morphological traits of the organ. The midgut tract is active at least ca. 12 h after hatching, as suggested by the presence of the peritrophic membrane in the lumen, the presence of abundant electro-dense vesicles in the cell apex, and the release of the vesicle content on the organ lumen. The midgut-hindgut junction forms an abrupt transition between the midgut tract and the hindgut tract in which epithelial cells with mixed features of midgut and hindgut do not occur.

Morphological and histological description of the midgut caeca in true crabs (Malacostraca: Decapoda: Brachyura): origin, development and potential role.

BACKGROUND: The decapods are a major group of crustaceans that includes shrimps, prawns, crayfishes, lobsters, and crabs. Several studies focused on the study of the digestive system of the decapods, constituted by the oesophagus, stomach, midgut tract, midgut gland, and hindgut. Nevertheless, in the midgut tract there are associated a set of organs called "midgut caeca", which are among the most controversial and less studied digestive organs of this group. This work used the common spider crab Maja brachydactyla Balss, 1922 as a model to resolve the origin, development, and potential role of the midgut caeca. Such organs were studied in the larvae (zoea I, zoea II, megalopa), first juveniles, and adult phases, being employed traditional and modern techniques: dissection, micro-computed tomography (Micro-CT), and light and electron microscopical analyses (TEM and SEM). RESULTS: The common spider crab has a pair of anterior midgut caeca and a single posterior caecum that originate from the endoderm germ layer: they develop from the midgut tract, and their epithelium is composed by secretory cells while lacking a cuticle lining. The midgut caeca are small buds in the newly hatched larvae, enlarge linearly during the larval development, and then continue growing until became elongated and coiled blind-tubules in adults. The adult midgut caeca are internally folded to increase their inner surface. The electron microscopy observations showed that the midgut caeca are highly active organs with important macroapocrine and microapocrine secretory activity. Our results suggest that the role of the caeca might be related to the digestive enzyme secretion. The secretory activity should increase as the animal grows in size. CONCLUSION: The present study resolves the embryonic origin of the midgut caeca (endoderm derived organs), development (general lengthening starting from small buds), and role (active secretory organs). The secretory activity of the midgut caeca should be incorporated in the current models of the digestive physiology in different decapod taxa.

Pathogenicity and virulence of hepatitis A virus.

Hepatitis A is an acute infection of the liver, which is mostly asymptomatic in children and increases the severity with age. Although in most patients the infection resolves completely, in a few of them it may follow a prolonged or relapsed course or even a fulminant form. The reason for these different outcomes is unknown, but it is generally accepted that host factors such as the immunological status, age and the occurrence of underlaying hepatic diseases are the main determinants of the severity. However, it cannot be ruled out that some virus traits may also contribute to the severe clinical outcomes. In this review, we will analyze which genetic determinants of the virus may determine virulence, in the context of a paradigmatic virus in terms of its genomic, molecular, replicative, and evolutionary features.

Description of the larval and adult hindgut tract of the common spider crab Maja brachydactyla Balss, 1922 (Brachyura, Decapoda, Malacostraca).

Arthropods are the most diversified animals on Earth. The morphology of the digestive system has been widely studied in insects; however, crustaceans have received comparatively little attention. This study describes the hindgut tract of the common spider crab Maja brachydactyla Balss, 1922, in larvae and adults using dissection, light and electron microscopical analyses. The hindgut tract maintains a similar general shape in larvae and adults. Major differences among stages are found in the morphology of epithelial cells and microspines, the thickness of the cuticle and connective-like tissue, and the presence of rosette glands (only in adults). Here, we provide the description of the sub-cellular structure of the folds, epithelium (conformed by tendon cells), musculature, and microspines of the hindgut of larvae and adults of M. brachydactyla. The morphological features of the hindgut of M. brachydactyla are compared with those of other arthropods (Insecta, Myriapoda and Arachnida). Our results suggest that the morphology of the hindgut is associated mainly with transport of faeces. In adults, the hindgut may also exert an osmoregulatory function, as described in other arthropods. At difference from holometabolous insets, the hindgut of M. brachydactyla (Decapoda) does not undergo a true metamorphic change during development, but major changes observed between larval and adult stages might respond to the different body size between life stages.

Traditional Games as Cultural Heritage: The Case of Canary Islands (Spain) From an Ethnomotor Perspective.

UNESCO in the 2030 agenda for sustainable development establishes respect for the environment and sustainability education as key elements for the challenges of society in the coming years. In the educational context, physical education can have a vital role in sustainability education, through Traditional Sporting Games (TSG). The aim of this research was to study from an ethnomotor perspective the different characteristics of two different groups of TSG (with and without objects) in the Canary Islands, Spain. The corpus of this investigation was made up of 513 TSG, identified by two analysis techniques and collected in a database. The categories corresponding to the variables of the internal logic of the game were the type of motor interaction, related to space, relationships with time (competition), and relationships with objects. The study also examined the variables of external logic or sociocultural conditions such as the protagonists, playing areas, and game moments. The data analysis was carried out using descriptive and inferential statistics: cross-tables, effect sizes, classification trees (CHAID), and the identification of frequency areas. Of the total number of playful activities identified (n = 664), most were physical activities (n = 513/664; 77.26%) (non-physical activities: n = 151/664; 22.74%). These activities were Quasi-games without rules (n = 87) and TSG (n = 426) as well as activities with Objects (n = 299) and without material (n = 214). This research confirms that the TSG in the Canary Islands is a mirror of traditional culture and, from a pedagogical approach, shows great potential for material and social sustainability.

Playing Ludomotor Activities in Lleida During the Spanish Civil War: An Ethnomotor Approach.

The traditional ludomotor activities (LA) are recognized by UNESCO as an intangible piece of cultural heritage. The ethnomotricity analyzes LA in its sociocultural context, taking into account the proprieties of rules or motor conditions (internal logic) and the link with local culture (external logic). The aim of this research was to identify and reveal the distinctive ethnomotor features of LA in order to understand the adaptations that occurred in the social scenario of the Spanish Civil War (1936-1939) in Lleida. The corpus of the research was constituted by 101 LA which were collected from the analysis of 20 semi-structured interviews. An "ad hoc" tool was designed and agreed upon by expert observers. It was comprised of a total of 27 ethnomotor variables related to LA. The experts achieved high reliability [Cohen's kappa coefficient (κ) and Spearman's correlation coefficient = 1] when the classification of LA was carried out on two different occasions. Descriptive statistics, cross-tabulations (Pearson's chi-squared) effect sizes, and two-step clusters were performed by external and internal logic variables. The presence or absence of motor interaction (X 2 = 9.029; df = 1; p < 0.003; ES = 0.298) was enlightening when comparing LA with and without a war connotation. On the other hand, the hierarchy of variables rested primarily on IL-Domain (Psycho-Coop-Oppo-Coop/Oppo) (PI = 1). Among other singularities, while two-step cluster analysis revealed a corresponding ethnomotor silhouette with cluster 1, with the warlike connotation (n = 48; 96.0%), its homologous structure was expressed (Cluster 2) in the absence of the warlike character (n = 26; 50%).

The Critical Role of Codon Composition on the Translation Efficiency Robustness of the Hepatitis A Virus Capsid.

Hepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype-phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype-phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff-not naturally occurring in HAV infection-involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.

Human Astrovirus MLB Replication In Vitro: Persistence in Extraintestinal Cell Lines.

MLB astroviruses were identified 10 years ago in feces from children with gastroenteritis of unknown etiology and have been unexpectedly detected in severe cases of meningitis/encephalitis, febrile illness of unknown etiology, and respiratory syndromes. The aim of this study was to establish a cell culture system supporting MLB astrovirus replication. We used two clinical strains to infect several cell lines, an MLB1 strain from a gastroenteritis case, and an MLB2 strain associated with a neurologic infection. Efforts to propagate the viruses in the Caco-2 cell line were unsuccessful. In contrast, we identified two human nonintestinal cell lines, Huh-7 and A549, permissive for both genotypes. After serial passages in the Huh-7.5 cell line, the adapted strains were able to establish persistent infections in the Huh-7.5, Huh-7AI, and A549 cell lines, with high viral loads (up to 10 log10 genome copies/ml) detected by quantitative reverse transcription-PCR (RT-qPCR) in the culture supernatant. Immunofluorescence assays demonstrated infection in about 10% of cells in persistently infected cultures. Electron microscopy revealed particles of 32 to 33 nm in diameter after negative staining of cell supernatants and capsid arrays in ultrathin sections with a particularly high production in Huh-7.5 cells. Interferon (IFN) expression by infected cells and effect of exogenous IFN varied depending on the type of infection and the cell line. The availability of a cell culture system to propagate MLB astroviruses represents a key step to better understand their replicative cycle, as well as a source of viruses to conduct a wide variety of basic virologic studies.IMPORTANCE MLB astroviruses are emerging viruses infecting humans. More studies are required to determine their exact epidemiology, but several reports have already identified them as the cause of unexpected clinical diseases, including severe neurologic diseases. Our study provides the first description of a cell culture system for the propagation of MLB astroviruses, enabling the study of their replicative cycle. Moreover, we demonstrated the unknown capacity of MLB astrovirus to establish persistent infections in cell culture. Whether these persistent infections are also established in vivo remains unknown, but the clinical consequences would be of high interest if persistence was confirmed in vivo Finally, our analysis of IFN expression provides some trails to understand the mechanism by which MLB astroviruses can cause persistent infections in the assayed cultures.

Structure of the stomach cuticle in adult and larvae of the spider crab Maja brachydactyla (Brachyura, Decapoda).

The stomach of decapods is a complex organ with specialized structures that are delimited by a cuticle. The morphology and ontogeny of the stomach are largely described, but few studies have focused on the morphology of its cuticle. This study examined the morphology of the stomach cuticle of cardiac sacs, gastric mill ossicles, cardio-pyloric valve and pyloric filters, and during various stages (zoea I and II, megalopa, first juvenile, and adult) of the common spider crab Maja brachydactyla using dissection, histology and transmission electron microscopy. The results show that cuticle morphology varies among structures (e.g., cardiac sacs, urocardiac ossicle, cardio-pyloric valve, pyloric filters), within a single structure (e.g., different sides of the urocardiac ossicle) and among different life stages. The cuticle during the larval stages is very thin and the different layers (epicuticle, exocuticle, and endocuticle) are infrequently distinguishable by histology. Major changes during larval development regarding cuticle morphology are observed after the molt to megalopa, including the increment in thickness in the gastric mill ossicles and cardio-pyloric valve, and the disappearance of the long thickened setae of the cardio-pyloric valve. The cuticle of all the stomach structures in the adults is thicker than in larval and juvenile stages. The cuticle varies in thickness, differential staining affinity and morphology of the cuticle layers. The structure-function relationship of the cuticle morphology is discussed.

Morphology and ultrastructure of the midgut gland ("hepatopancreas") during ontogeny in the common spider crab Maja brachydactyla Balss, 1922 (Brachyura, Majidae).

We studied the anatomy and cytology of the midgut gland (MGl) of the common spider crab Maja brachydactyla Balss, 1922 at several life stages (zoea, megalopa, first juvenile, and adult) using dissection, histology, electron microscopy, computed tomography, and micro-computed tomography (micro-CT). In newly hatched larvae, 14 blind-end tubules form the MGl. The length of the tubules increases during the larval development. In the late megalopa, the number of tubules also increases. In adults, 35,000 to 60,000 blind-ending tubules comprise the MGl. In all life stages, a square-net network of muscle fibers surround the tubules. We describe five cell types in the MGl in all larval stages, which have a similar location, histology, and ultrastructure in larvae and adults: embryonary (E-) cells, resorptive (R-) cells, fibrillar (F-) cells, blister-like (B-) cells, and midget (M-) cells. Major difference between larval and adult cells is the larger size of the adult cells. Microapocrine secretion occurs from the microvilli of the B-cells. No ultrastructural changes were observed during larval development, which suggests that the function of each cell type might be similar in all life stages. The role of each epithelial cell type in larvae and adults is discussed.

Micro-computed tomography and histology to explore internal morphology in decapod larvae.

Traditionally, the internal morphology of crustacean larvae has been studied using destructive techniques such as dissection and microscopy. The present study combines advances in micro-computed tomography (micro-CT) and histology to study the internal morphology of decapod larvae, using the common spider crab (Maja brachydactyla Balss, 1922) as a model and resolving the individual limitations of these techniques. The synergy of micro-CT and histology allows the organs to be easily identified, revealing simultaneously the gross morphology (shape, size, and location) and histological organization (tissue arrangement and cell identification). Micro-CT shows mainly the exoskeleton, musculature, digestive and nervous systems, and secondarily the circulatory and respiratory systems, while histology distinguishes several cell types and confirms the organ identity. Micro-CT resolves a discrepancy in the literature regarding the nervous system of crab larvae. The major changes occur in the metamorphosis to the megalopa stage, specifically the formation of the gastric mill, the shortening of the abdominal nerve cord, the curving of the abdomen beneath the cephalothorax, and the development of functional pereiopods, pleopods, and lamellate gills. The combination of micro-CT and histology provides better results than either one alone.

Morphology and ultrastructure of the esophagus during the ontogeny of the spider crab Maja brachydactyla (Decapoda, Brachyura, Majidae).

The esophagus of the eucrustaceans is known as a short tube that connects the mouth with the stomach but has generally received little attention by the carcinologists, especially during the larval stages. By this reason, the present study is focused on the morphology and ultrastructure of the esophagus in the brachyuran Maja brachydactyla during the larval development and adult stage. The esophagus shows internally four longitudinal folds. The simple columnar epithelium is covered by a thick cuticle. The epithelial cells of the adults are intensively interdigitated and show abundant apical mitochondria and bundles of filamentous structures. The cuticle surface has microspines and mutually exclusive pores. Three muscle layers surrounded by the connective tissue are reported: circular muscles forming a broad continuous band, longitudinal muscle bundles adjacent to the circular muscles, and dilator muscles crossing the connective tissue vertically toward the epithelium. The connective tissue has rosette glands. The esophagus of the larvae have epithelial cells with big vesicles but poorly developed interdigitations and filamentous structures, the cuticle is formed by a procuticle without differentiated exocuticle and endocuticle, the connective layer is thin and the rosette glands are absent. The observed features can be explained by his role in the swallowing of the food.

Improving virus production through quasispecies genomic selection and molecular breeding.

Virus production still is a challenging issue in antigen manufacture, particularly with slow-growing viruses. Deep-sequencing of genomic regions indicative of efficient replication may be used to identify high-fitness minority individuals suppressed by the ensemble of mutants in a virus quasispecies. Molecular breeding of quasispecies containing colonizer individuals, under regimes allowing more than one replicative cycle, is a strategy to select the fittest competitors among the colonizers. A slow-growing cell culture-adapted hepatitis A virus strain was employed as a model for this strategy. Using genomic selection in two regions predictive of efficient translation, the internal ribosome entry site and the VP1-coding region, high-fitness minority colonizer individuals were identified in a population adapted to conditions of artificially-induced cellular transcription shut-off. Molecular breeding of this population with a second one, also adapted to transcription shut-off and showing an overall colonizer phenotype, allowed the selection of a fast-growing population of great biotechnological potential.

Foregut morphology and ontogeny of the spider crab Maja brachydactyla (Brachyura, Majoidea, Majidae).

We describe the morphology of the foregut of the spider crab Maja brachydactyla Balss, 1922, from first larval stage to adult, with detailed stage-specific documentation using light and scanning electron microscopy. A total of 40 ossicles have been identified in the foregut of adults of M. brachydactyla using Alizarin-Red staining. The morphological pattern of the ossicles and gastric mill is very similar to other Majoidea species with only a few variations. The foregut of the zoeae stages appeared as a small and simple cavity, with a cardio-pyloric valve that separates the stomach into cardiac and pyloric regions. The pyloric filter is present from the first zoea, in contrast to the brachyuran species which have an extended larval development. Calcified structures have been identified in the cardio-pyloric valve and pyloric region of the zoeal stages. The most significant changes in foregut morphology take place after the metamorphosis from ZII to megalopa, including the occurrence of the gastric mill. In the megalopa stage, the foregut ossicles are recognizable by their organization and general morphology, but are different from the adult phase in shape and number. Moreover, the gastric teeth show important differences: the cusps of the lateral teeth are sharp (no molariform); the dorsal tooth have a small, dentate cusp (not a well-developed quadrangular cusp); and the accessory teeth are composed of one sharp peak (instead of four sharp peaks). The gastric mill ontogeny from megalopa to adult reveals intermediate morphologies during the earlier juvenile stages. The relationship between gastric mill structures with food preferences and their contribution to the brachyuran phylogeny are briefly discussed.

Foregut morphology and ontogeny of the mud crab Dyspanopeus sayi (Smith, 1869) (Decapoda, Brachyura, Panopeidae).

The morphology of the foregut of the Say's mud crab Dyspanopeus sayi was described in adults and larvae. The ossicle system was illustrated based on a staining method with Alizarin-Red. The gastric teeth and cardio-pyloric valve were dissected and examined using optical and scanning electron microscopy. In the adults, the morphology of ossicles and gastric teeth of D. sayi is very similar to the related species Rhithropanopeus harrisii. The foregut of first zoea (ZI) presented a functional cardio-pyloric valve while the filter press was lacking. The filter press was observed in the pyloric chamber from ZII. The most significant changes in morphology take place after metamorphosis from ZIV to megalopa, including the occurrence of the gastric mill. The organization and morphology of many megalopal foregut ossicles are recognizable in the adult phase, although the morphology of the gastric teeth differs from the morphology of adults. A correlation of gastric mill structures with food preferences and their contribution to the phylogeny are briefly discussed.

Hepatitis A virus adaptation to cellular shutoff is driven by dynamic adjustments of codon usage and results in the selection of populations with altered capsids.

UNLABELLED: Hepatitis A virus (HAV) has a highly biased and deoptimized codon usage compared to the host cell and fails to inhibit host protein synthesis. It has been proposed that an optimal combination of abundant and rare codons controls the translation speed required for the correct capsid folding. The artificial shutoff host protein synthesis results in the selection of variants containing mutations in the HAV capsid coding region critical for folding, stability, and function. Here, we show that these capsid mutations resulted in changes in their antigenicity; in a reduced stability to high temperature, low pH, and biliary salts; and in an increased efficacy of cell entry. In conclusion, the adaptation to cellular shutoff resulted in the selection of large-plaque-producing virus populations. IMPORTANCE: HAV has a naturally deoptimized codon usage with respect to that of its cell host and is unable to shut down the cellular translation. This fact contributes to the low replication rate of the virus, in addition to other factors such as the highly inefficient internal ribosome entry site (IRES), and explains the outstanding physical stability of this pathogen in the environment mediated by a folding-dependent highly cohesive capsid. Adaptation to artificially induced cellular transcription shutoff resulted in a redeoptimization of its capsid codon usage, instead of an optimization. These genomic changes are related to an overall change of capsid folding, which in turn induces changes in the cell entry process. Remarkably, the adaptation to cellular shutoff allowed the virus to significantly increase its RNA uncoating efficiency, resulting in the selection of large-plaque-producing populations. However, these populations produced much-debilitated virions.

A single mutation in the glycophorin A binding site of hepatitis A virus enhances virus clearance from the blood and results in a lower fitness variant.

Hepatitis A virus (HAV) has previously been reported to bind to human red blood cells through interaction with glycophorin A. Residue K221 of VP1 and the surrounding VP3 residues are involved in such an interaction. This capsid region is specifically recognized by the monoclonal antibody H7C27. A monoclonal antibody-resistant mutant with the mutation G1217D has been isolated. In the present study, the G1217D mutant was characterized physically and biologically in comparison with the parental HM175 43c strain. The G1217D mutant is more sensitive to acid pH and binds more efficiently to human and rat erythrocytes than the parental 43c strain. In a rat model, it is eliminated from serum more rapidly and consequently reaches the liver with a certain delay compared to the parental 43c strain. In competition experiments performed in vivo in the rat model, the G1217D mutant was efficiently outcompeted by the parental 43c strain. Only in the presence of antibodies reacting specifically with the parental 43c strain could the G1217D mutant outcompete the parental 43c strain in serum, although the latter still showed a remarkable ability to reach the liver. Altogether, these results indicate that the G1217D mutation induces a low fitness phenotype which could explain the lack of natural antigenic variants of the glycophorin A binding site.

Hepatitis A virus evolution and the potential emergence of new variants escaping the presently available vaccines.

Hepatitis A is the most common infection of the liver worldwide and is fecal-orally transmitted. Its incidence tends to decrease with improvements in hygiene conditions but at the same time its severity increases. Hepatitis A virus is the causative agent of acute hepatitis in humans and belongs to the Hepatovirus genus in the Picornaviridae family, and it has very unique characteristics. This article reviews some molecular and biological properties that allow the virus to live in a very quiescent way and to build an extremely stable capsid that is able to persist in and out of the body. Additionally, the relationship between the genomic composition and the structural and antigenic properties of the capsid is discussed, and the potential emergence of antigenic variants is evaluated from an evolutionary perspective.

Internal anatomy and ultrastructure of the male reproductive system of the Norway lobster Nephrops norvegicus (Decapoda: Astacidea).

The Norway lobster (Nephrops norvegicus) is economically important in Europe. However, apart from the female reproductive system, very little is known about its internal anatomy. This article focuses on studying the internal anatomy and ultrastructure of the male reproductive system. This system follows the general pattern found among decapod crustaceans, with several peculiarities. Testes are composed of lobular sperm ducts in which the spermatozoa are fully constituted. The spermatozoa present three lateral arms and a long acrosome, which gives a false appearance of flagellated spermatozoa. The two testes form a double H under the heart, and the vas deferens (VD) arise from each side at the posterior edge of the double H. The main characteristic of the VD is the presence of a sphincter in the enlarged area of the distal end of the middle VD. The MVD here shows an increase in musculature of the wall as compared to the VD, which regulates the passage of the sperm cord to the distal VD (DVD) and thence to the thelycum of the female. The wall of the spermatophore is formed in the distal part of the proximal VD, which surrounds the unique sperm cord present in the VD. Isolated spermatophores are not observed in the VD. The sperm cord is pinched off during copulation by the musculature of the DVD. Then, a portion of the sperm cord is transferred from each VD to form the isolated spermatophores. The wall of the spematophores and the spermatozoa that are observed inside the thelycum have the same morphology as those observed in the VD.

Fine-tuning translation kinetics selection as the driving force of codon usage bias in the hepatitis A virus capsid.

Hepatitis A virus (HAV), the prototype of genus Hepatovirus, has several unique biological characteristics that distinguish it from other members of the Picornaviridae family. Among these, the need for an intact eIF4G factor for the initiation of translation results in an inability to shut down host protein synthesis by a mechanism similar to that of other picornaviruses. Consequently, HAV must inefficiently compete for the cellular translational machinery and this may explain its poor growth in cell culture. In this context of virus/cell competition, HAV has strategically adopted a naturally highly deoptimized codon usage with respect to that of its cellular host. With the aim to optimize its codon usage the virus was adapted to propagate in cells with impaired protein synthesis, in order to make tRNA pools more available for the virus. A significant loss of fitness was the immediate response to the adaptation process that was, however, later on recovered and more associated to a re-deoptimization rather than to an optimization of the codon usage specifically in the capsid coding region. These results exclude translation selection and instead suggest fine-tuning translation kinetics selection as the underlying mechanism of the codon usage bias in this specific genome region. Additionally, the results provide clear evidence of the Red Queen dynamics of evolution since the virus has very much evolved to re-adapt its codon usage to the environmental cellular changing conditions in order to recover the original fitness.