Corrigendum: Dual Host and Pathogen RNA-Seq Analysis Unravels Chicken Genes Potentially Involved in Resistance to Highly Pathogenic Avian Influenza Virus Infection.

[This corrects the article DOI: 10.3389/fimmu.2021.800188.].

Dual Host and Pathogen RNA-Seq Analysis Unravels Chicken Genes Potentially Involved in Resistance to Highly Pathogenic Avian Influenza Virus Infection.

Highly pathogenic avian influenza viruses (HPAIVs) cause severe systemic disease and high mortality rates in chickens, leading to a huge economic impact in the poultry sector. However, some chickens are resistant to the disease. This study aimed at evaluating the mechanisms behind HPAIV disease resistance. Chickens of different breeds were challenged with H7N1 HPAIV or clade 2.3.4.4b H5N8 HPAIV, euthanized at 3 days post-inoculation (dpi), and classified as resistant or susceptible depending on the following criteria: chickens that presented i) clinical signs, ii) histopathological lesions, and iii) presence of HPAIV antigen in tissues were classified as susceptible, while chickens lacking all these criteria were classified as resistant. Once classified, we performed RNA-Seq from lung and spleen samples in order to compare the transcriptomic signatures between resistant and susceptible chickens. We identified minor transcriptomic changes in resistant chickens in contrast with huge alterations observed in susceptible chickens. Interestingly, six differentially expressed genes were downregulated in resistant birds and upregulated in susceptible birds. Some of these genes belong to the NF-kappa B and/or mitogen-activated protein kinase signaling pathways. Among these six genes, the serine protease-encoding gene PLAU was of particular interest, being the most significantly downregulated gene in resistant chickens. Expression levels of this protease were further validated by RT-qPCR in a larger number of experimentally infected chickens. Furthermore, HPAIV quasi-species populations were constructed using 3 dpi oral swabs. No substantial changes were found in the viral segments that interact with the innate immune response and with the host cell receptors, reinforcing the role of the immune system of the host in the clinical outcome. Altogether, our results suggest that an early inactivation of important host genes could prevent an exaggerated immune response and/or viral replication, conferring resistance to HPAIV in chickens.

Pathobiology of the highly pathogenic avian influenza viruses H7N1 and H5N8 in different chicken breeds and role of Mx 2032 G/A polymorphism in infection outcome.

Chickens are highly susceptible to highly pathogenic avian influenza viruses (HPAIVs). However, the severity of infection varies depending of the viral strain and the genetic background of the host. In this study, we evaluated the pathogenesis of two HPAIVs (H7N1 and H5N8) and assessed the susceptibility to the infection of local and commercial chicken breeds from Spain. Eight chicken breeds were intranasally inoculated with 105 ELD50 of A/Chicken/Italy/5093/1999 (H7N1) or A/Goose/Spain/IA17CR02699/2017 (H5N8 clade 2.3.4.4. B) and monitored during 10 days. Chickens were highly susceptible to both HPAIVs, but H7N1 was considerably more virulent than H5N8 as demonstrated by the highest mortality rates and shortest mean death times (MDT). Both HPAIVs produced severe necrosis and intense viral replication in the central nervous system, heart and pancreas; however, the lesions and replication in other tissues were virus-dependent. High levels of viral RNA were detected by the oral route with both viruses. In contrast, a low number of H5N8-inoculated chickens shed by the cloacal route, demonstrating a different pattern of viral shedding dependent of the HPAIV. We found a high variation in the susceptibility to HPAIVs between the different chicken breeds. The birds carrying the genotype AA and AG at position 2032 in chicken Mx gene presented a slightly higher, but not significant, percentage of survival and a statistically significant longer MDT than GG individuals. Our study demonstrated that the severity of HPAI infection is largely dependent of the viral isolate and host factors, underlining the complexity of HPAI infections.

Association Between the Brain-derived Neurotrophic Factor Val66Met Polymorphism and Overweight/Obesity in Pediatric Population.

BACKGROUND: The brain-derived neurotrophic factor (BDNF) rs6265 (G196A; Val66Met) single nucleotide polymorphism has been associated with BMI and obesity in distinct populations, both adult and pediatric, with contradictory results involving either Val or Met as the risk variant. AIM OF THE STUDY: To determine the association between the BDNF Val66Met polymorphism and BMI in Mexican children and adolescents. METHODS: BDNF Val66Met genotyping by restriction fragment length polymorphism and nutritional status characterized by their BMI-for-age z-scores (BAZ) from pediatric volunteers (n = 498) were analyzed by Fisher's exact test association analysis. Standardized residuals (R) were used to determine which genotype/allele had the major influence on the significant Fisher's exact test statistic. Odds ratios were analyzed to measure the association between genotype and normal weight (≥-2 SD < + 1 SD) and overweight (≥ + 1 SD, including obesity, Ow + Ob) status with 95% confidence intervals to estimate the precision of the effect as well as 95% credible intervals to obtain the most probable estimate. RESULTS: Comparisons between GG (Val/Val), GA (Val/Met) and AA (Met/Met) genotypes or Met homozygotes vs. Val carriers (combination of GG and GA genotypes) showed significant differences (p = 0.034 and p = 0.037, respectively) between normal weight and the combined overweight and obese pediatric subjects. Our data showed that children/adolescents homozygous for the A allele have increased risk of overweight compared to the Val carriers (Bayes OR = 4.2, 95% CI**[1.09-33.1]). CONCLUSION: This is the first study showing the significant association between the BDNF rs6265 AA (Met/Met) genotype and overweight/obesity in Mexican pediatric population.

Coexisting role of fasting or feeding and dietary lipids in the control of gene expression of enzymes involved in the synthesis of saturated, monounsaturated and polyunsaturated fatty acids.

In the liver, maintaining lipid homeostasis is regulated by physiological and exogenous factors. These lipids are synthesized by Fasn, elongases and desaturases. Interactions in an organism among these factors are quite complex and, to date, relatively little is known about them. The aim of this study was to evaluate the coexisting role of physiological (insulin, fasting and feeding) and exogenous (dietary lipids) factors in the control of gene expression of Fasn, elongases and desaturases via Srebf-1c in liver from rats. Gene expression of encoding enzymes for fatty acid synthesis and fatty acid composition was evaluated in liver from rats in fasting and feeding (at 30, 60, 90 and 120 min after feeding) when food intake (adequate or high-lipid diet) was synchronized to a restricted period of 7h. Fasn, Scd and Fads2 were induced during 120 min after initial feeding in both dietary groups. This induction may be activated in part by insulin via Srebf-1c. Also, we showed for the first time that Elovl7 may be regulated by insulin and dietary lipids. The failure to synthesize saturated and monounsaturated fatty acids is consistent with a downregulation of Fasn and Scd, respectively, by dietary lipids. A higher content of LC-PUFAs was observed due to a high expression of Elovl2 and Elovl5, although Fads2 was suppressed by dietary lipids. Therefore, elongases may have a mechanism that is Srebf-1c-independent. This study suggests that a high-lipid diet triggers, during 120 min after initial feeding, a tight coordination among de novo lipogenesis, elongation, and desaturation and may not always be regulated by Srebf-1c. Finally, upregulation by feeding (insulin) of Fasn, Scd, Fads2 and Srebf-1c is insufficient to compensate for the inhibitory effect of dietary lipids.