Weak SARS-CoV-2-specific responses of TIGIT-expressing CD8^(+)T cells in people living with HIV after a third dose of a SARS-CoV-2 inactivated vaccine

Background:T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains(TIGIT),an inhibitory receptor expressed on T cells,plays a dysfunctional role in antiviral infection and antitumor activity.However,it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)inactivated vaccines.Methods:Forty-five people living with HIV(PLWH)on antiretroviral therapy(ART)for more than two years and 31 healthy controls(HCs),all received a third dose of a SARS-CoV-2 inactivated vaccine,were enrolled in this study.The amounts,activation,proportion of cell subsets,and magnitude of the SARS-CoV-2-specific immune response of TIGIT^(+)CD4^(+)and TIGIT^(+)CD8^(+)T cells were investigated before the third dose but 6 months after the second vaccine dose(0W),4 weeks(4W)and 12 weeks(12W)after the third dose.Results:Compared to that in HCs,the frequency of TIGIT^(+)CD8^(+)T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine,and the immune activation of TIGIT^(+)CD8^(+)T cells also increased.A decrease in the ratio of both T naïve(T_(N))and central memory(T_(CM))cells among TIGIT^(+)CD8^(+)T cells and an increase in the ratio of the effector memory(T_(EM))subpopulation were observed at 12W in PLWH.Interestingly,particularly at 12W,a higher proportion of TIGIT^(+)CD8^(+)T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay.Compared with 0W,SARS-CoV-2-specific TIGIT^(+)CD8^(+)T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs.Additionally,at all time points,the SARS-CoV-2-specific responses of TIGIT^(+)CD8^(+)T cells in PLWH were significantly weaker than those of TIGIT-CD8^(+)T cells.However,in HCs,the difference in the SARS-CoV-2-specific responses induced between TIGIT^(+)CD8^(+)T cells and TIGIT-CD8^(+)T cells was insignificant at 4W and 12W,except at 0W.Conclusions:TIGIT expression on CD8^(+)T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine,suggesting weakened resistance to SARS-CoV-2 infection,especially in PLWH.Furthermore,TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8^(+)T cells,thereby enhancing the effectiveness of vaccination.

Changing roles of CD3^(+)CD8^(low) T cells in combating HIV-1 infection

Background:Cluster of differentiation 8(CD8 T)cells play critical roles in eradicating human immunodeficiency virus(HIV)-1 infection,but little is known about the effects of T cells expressing CD8 at low levels(CD8^(low))or high levels(CD8^(high))on HIV-1 replication inhibition after HIV-1 invasion into individual.Methods:Nineteen patients who had been acutely infected with HIV-1(AHI)and 20 patients with chronic infection(CHI)for≥2 years were enrolled in this study to investigate the dynamics of the quantity,activation,and immune responses of CD3^(+)CD8^(low) T cells and their counterpart CD3^(+)CD8^(high) T cells at different stages of HIV-1 infection.Results:Compared with healthy donors,CD3^(+)CD8^(low) T cells expanded in HIV-1-infected individuals at different stages of infection.As HIV-1 infection progressed,CD3^(+)CD8^(low) T cells gradually decreased.Simultaneously,CD3^(+)CD8^(high) T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed.The classical activation of CD3^(+)CD8^(low) T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage.Meanwhile,activated CD38^(-)HLA-DR^(+)CD8^(low) T cells did not increase in the first month of AHI,and the number of these cells was inversely associated with viral load(r=-0.664,P=0.004)but positively associated with the CD4 T-cell count(r=0.586,P=0.014).Increased programmed cell death protein 1(PD-1)abundance on CD3^(+)CD8^(low) T cells was observed from the 1st month of AHI but did not continue to be enhanced,while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domains(TIGIT)abundance increase was observed in the 12th month of infection.Furthermore,increased PD-1 and TIGIT abundance on CD3^(+)CD8^(low) T cells was associated with a low CD4 T-cell count(PD-1:r=-0.456,P=0.043;TIGIT:r=-0.488,P=0.029)in CHI.Nonetheless,the nonincrease in PD-1 expression on classically activated CD3^(+)CD8^(low) T cells was inversely associated with HIV-1 viremia in the first month of AHI(r=-0.578,P=0.015).Notably,in the first month of AHI,few CD3^(+)CD8^(low) T cells,but comparable amounts of CD3^(+)CD8^(high) T cells,responded to Gag peptides.Then,weaker HIV-1-specific T-cell responses were induced in CD3^(+)CD8^(low) T cells than CD3^(+)CD8^(high) T cells at the 3rd and 12th months of AHI and in CHI.Conclusions:Our findings suggest that CD3^(+)CD8^(low) T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response.Subsequently,CD3^(+)CD8^(low) T-cell number decreased gradually as infection persisted,and their anti-HIV functions were inferior to those of CD3^(+)CD8^(high) T cells.

Dietary ribose supplementation improves flesh quality through purine metabolism in gibel carp(Carassius auratus gibelio)

Since the aquaculture industry is currently observing a deterioration in the flesh quality of farmed fish,the use of nutrients as additives to improve the flesh quality of farmed fish species is a viable strategy.The aim of this study was to investigate the effect of dietary D-ribose(RI)on the nutritional value,texture and flavour of gibel carp(Carassius auratus gibelio).Four diets were formulated containing exogenous RI at 4 gradient levels:0(Control),0.15%(0.15RI),0.30%(0.30RI)and 0.45%(0.45RI).A total of 240 fish(150±0.31 g)were randomly distributed into 12 fibreglass tanks(150 L per tank).Triplicate tanks were randomly assigned to each diet.The feeding trial was carried out in an indoor recirculating aquaculture system for 60 d.After the feeding trial,the muscle and liver of gibel carp were analysed.The results showed that RI supplementation did not result in any negative impact on the growth performance and 0.30RI supplementation significantly increased the whole-body protein content compared to the control group.The contents of collagen and glycogen in muscle were enhanced by RI supplementation.The alterations in the flesh indicated that RI supplementation improved the texture of the flesh in terms of its water-holding capacity and hardness,therefore improving the taste.Dietary RI facilitated the deposition of amino acids and fatty acids in the muscle that contributed to the meaty taste and nutritional value.Furthermore,a combination of metabolomics and expression of key genes in liver and muscle revealed that 0.30RI activated the purine metabolism pathways by supplementing the substrate for nucleotide synthesis and thereby promoting the deposition of flavour substance in flesh.This study offers a new approach for providing healthy,nutritious and flavourful aquatic products.

Effects of fish meal replacement with Chlorella meal on growth performance,pigmentation,and liver health of largemouth bass(Micropterus salmoides)

Chlorella meal is a potential protein source for aquafeeds.However,the physiological response of carnivorous fish fed Chlorella meal remains elusive.This study evaluated the effects of replacing dietary fish meal with Chlorella meal on growth performance,pigmentation,and liver health in largemouth bass.Five diets were formulated to replace dietary fish meal of 0%(C0,control),25%(C25),50%(C50),75%(C75),and 100%(C100)with Chlorella meal,respectively.Total 300 fish(17.6±0.03 g)were randomly assigned to 15 tanks(3 tanks/group).Fish were fed the experimental diet twice daily for 8 weeks.The increased dietary Chlorella meal quadratically influenced the final body weight(FBW),weight gain rate(WGR),specific growth rate(SGR),and feed intake(FI),which were significantly lower in the C100 group than in the other groups(P<0.05).The feed conversion ratio(FCR)increased linearly or quadratically with dietary Chlorella meal.Dietary Chlorella meal linearly or quadratically increased the lutein content of plasma,liver,and dorsal muscle of largemouth bass(P<0.05).Compared to the C0 group,all supplemented Chlorella meal groups significantly improved the yellowness(b*)of the dorsal body(1.5 to 2.0 fold),abdominal body(1.5 to 1.8 fold),and dorsal muscle(3.8 to 5.4 fold)of largemouth bass(P<0.05).In addition,compared to the C0 group,the liver vacuolation area of fish was significantly increased in the C75 and C100 groups(P<0.05).Transcriptional levels of apoptosis-related genes of b-cell lymphoma-2(bcl2),caspase-9-like(casp9),and caspase-3a(casp3)were markedly upregulated(0.9 to 1.6 fold)in the C100 group compared to the C0 group(P<0.05).Based on the quadratic regression analysis between FBW,WGR,or SGR and dietary Chlorella meal level,largemouth bass had the best growth when replacing 31.7%to 32.6%of fish meal with 15.03%to 15.43%dietary Chlorella meal.The present results indicated that dietary supplementation with Chlorella meal(11.85%to 47.45%)significantly enhanced the pigmentation;however,total replacement of fish meal(40%)with Chlorella meal(47.45%)caused growth retardation,apoptosis,and liver damage in largemouth bass.

Association of apolipoprotein E epsilon 4 and cognitive impairment in adults living with human immunodeficiency virus: a meta-analysis

Background: It is controversial whether the apolipoprotein E epsilon 4 allele (APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations betweenAPOE ε4 and cognitive impairment in people living with HIV (PLWH).Methods: Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations betweenAPOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains betweenAPOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical variables.Results: Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive impairment.APOE ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates [k] = 19,P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers (P = 0.015).APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = -0.51, 95% CI = [-0.76, -0.25],P < 0.001,k = 4,I^(2)= 0%), learning (SMD = -0.52, 95% CI = [-0.75, -0.28],P < 0.001,k = 5,I^(2) = 0%), executive function (SMD = -0.41, 95% CI= [-0.59, -0.23],P < 0.001,k= 8,I^(2)= 0%), memory (SMD=-0.41, 95% CI= [-0.61, -0.20],P < 0.001,k= 10,I^(2)= 36%), attention/working memory (SMD=-0.34, 95% CI= [-0.54, -0.14],P= 0.001,k= 6,I^(2)= 0%), speed of information processing (SMD = -0.34, 95% CI = [-0.53, -0.16],P < 0.001,k = 8,I^(2) = 0%), and motor function (SMD = -0.19, 95% CI = [-0.38, -0.01],P = 0.04,k = 7,I^(2) = 0%).Conclusions: Our meta-analysis provides significant evidence thatAPOE ε4 is a risk genotype for HIV-associated cognitive impairment, especially in cognitive domains of fluency, learning, executive function, and memory. Moreover, the impairment is sex specific.Meta analysis registration: PROSPERO, CRD 42021257775.

Genomic polymorphisms at the crhr2 locus improve feed conversion efficiency through alleviation of hypothalamus-pituitary-interrenal axis activity in gibel carp(Carassius gibelio)

Improvement in fish feed conversion efficiency(FCE)is beneficial for sustaining global food fish supplies.Here,we show that a set of polymorphisms at locus of the corticotropin releasing hormone receptor 2(crhr2),which is involved in hypothalamuspituitary-interrenal(HPI)axis signaling,is associated with improved FCE in farmed allogynogenetic gibel carp strain CAS Ⅲ compared with that in the wild gibel carp strain Dongting(DT).This set of polymorphisms downregulates the expression levels of crhr2 mRNA in the brain and pituitary tissues in gibel carp strain CAS Ⅲ compared with those in strain DT.Furthermore,compromised HPI axis signaling is observed in gibel carp strain CAS Ⅲ,such as decreased α-melanocyte stimulating hormone protein levels,plasma cortisol content,and stress responses.Moreover,enhanced activation of protein kinase B/mammalian target of rapamycin complex 1 signaling observed in the muscle tissue of strain CAS Ⅲ in comparison to that in strain DT indicated elevated anabolic metabolism in strain CAS Ⅲ.Thus,these studies demonstrate that the genetic markers associated with compromised HPI axis signaling,such as crhr2,are potentially useful for genetic selection toward improvement in farmed fish growth and FCE,which would reduce fishmeal consumption and thereby indirectly facilitate sustainable fisheries.

Advances in Research on COVID-19 Vaccination for People Living with HIV

Introduction In December 2019,multiple cases of aggravated pneumonia of unidentified origin were reported inWuhan,China.These were confirmed to be caused by a novel coronavirus.The World Health Organization(WHO)named the disease coronavirus disease 2019(COVID-19).The International Committee on Taxonomy of Viruses officially identified the novel virus severe acute respiratory syndrome coronavirus 2(SARSCoV-2).[1]Although China is now a low endemic areawith a downward trend in the number of confirmed and suspected cases,[2]the threat of the COVID-19 pandemic remains critical.By mid-March 2022,the cumulative number of reported confirmed cases of COVID-19 worldwide exceeded 450 million,with more than 6 million deaths.[3]Since there is no specific therapeutic drug for the treatment of COVID-19,it is important to control the epidemic by actively promoting SARS-CoV-2 vaccination globally,reducing the risk of viral transmission and the incidence of severe COVID-19,thus improving prognoses.[4]