Host immunogenetics in tick-borne encephalitis virus infection—The CCR5 crossroad

Ellwanger, Joel Henrique

doi:10.1016/j.ttbdis.2019.03.005

Cited by 16 publications

(12 citation statements)

References 164 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The nonredundancy of CCR5 is relevant especially for infections by neuroinvasive flaviviruses (Bardina and Lim, 2012). For example, the absence of CCR5 due to CCR5Δ32 is considered deleterious in WNV infection (Glass et al, 2006;Lim et al, 2008) and in some aspects of TBEV infection (Ellwanger and Chies, 2019a). The non-redundant role of CCR5 is also likely in JEV infection (Larena et al, 2012).…”

Section: Ccr5 Gene Editing and Ccr5 Modulation: What Would Be The Effmentioning

confidence: 99%

“…Studies involving HIV will not be included in this article because different aspects of the relationship between HIV and CCR5/CCR5Δ32 are well established and have already been intensely explored in different reviews (Allen et al, 2018;Brelot and Chakrabarti, 2018;Ndung'u et al, 2019). Also, the impacts of CCR5 and CCR5Δ32 on tickborne encephalitis virus (TBEV) infection will not be addressed in this article because our group has recently reviewed these topics in a recent publication (Ellwanger and Chies, 2019a).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

et al. 2020

Self Cite

View full text Add to dashboard Cite

The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human CC chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in "CCR5 research" are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed.

show abstract

Section: Ccr5 Gene Editing and Ccr5 Modulation: What Would Be The Effmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite varying information due probably to ethnicity effects (Lee et al , ; Schauren et al , ), further complicated in admixed populations (Toson et al , ), epidemiological studies support the ccr5 Δ32 allele as a marker for good prognosis for these overreactive immune diseases (Vangelista & Vento, ). In contrast, ccr5 Δ32 homozygotes are prone to fatal infections by several pathogens such as influenza, West Nile, and tick‐borne encephalitis viruses (Lim & Murphy, ; Falcon et al , ; Ellwanger & Chies, ). The mechanisms by which the ccr5 Δ32 polymorphism affects all these pathologies have usually been linked to the capacity of CCR5 to regulate leukocyte trafficking.…”

Section: Introductionmentioning

confidence: 99%

CCR 5 deficiency impairs CD 4 ⁺ T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis

et al. 2020

View full text Add to dashboard Cite

CCR5 is not only a coreceptor for HIV‐1 infection in CD4+ T cells, but also contributes to their functional fitness. Here, we show that by limiting transcription of specific ceramide synthases, CCR5 signaling reduces ceramide levels and thereby increases T‐cell antigen receptor (TCR) nanoclustering in antigen‐experienced mouse and human CD4+ T cells. This activity is CCR5‐specific and independent of CCR5 co‐stimulatory activity. CCR5‐deficient mice showed reduced production of high‐affinity class‐switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD4+ T‐cell response. This study identifies a CCR5 function in the generation of CD4+ T‐cell memory responses and establishes an antigen‐independent mechanism that regulates TCR nanoclustering by altering specific lipid species.

show abstract

“…CCR5 is a type of CC chemokine receptor that belongs to the G protein-coupled receptor family and consists of three extracellular loops and three intracellular loops [25]. As reported, bone marrow-derived lymphocytes differentiate into mature functional CD4 + T cells in the thymus and then migrate to secondary lymphoid organs such as the spleen and lymph nodes.…”

Section: Discussionmentioning

confidence: 97%

Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

Zhang

Liang

Xie

et al. 2020

Mediators of Inflammation

View full text Add to dashboard Cite

Asthma is a heterogeneous chronic inflammatory disorder of the airways with a complex etiology, which involves a variety of cells and cellular components. Therefore, the aim of the study was to investigate the effects and mechanisms of antagonistic peptides that specifically bind to the first and second extracellular loops of CCR5 (GH and HY peptides, respectively) and anti-interleukin-23 subunit p19 (anti-IL-23p19) in the airway and thereby mediate inflammation and the IL-23/T helper 17 (Th17) cell pathway in asthmatic mice. An experimental asthma model using BALB/c mice was induced by ovalbumin (OVA) and treated with peptides that are antagonistic to CCR5 or with anti-IL-23p19. The extents of the asthmatic inflammation and mucus production were assessed. In addition, bronchoalveolar lavage fluid (BALF) was collected, the cells were counted, and the IL-4 level was detected by ELISA. The IL-23/Th17 pathway-related protein and mRNA levels in the lung tissues were measured, and the positive production rates of Th17 cells in the thymus, spleen, and peripheral blood were detected. The groups treated with one of the two peptides and/or anti-IL-23p19 showed significant reductions in allergic inflammation and mucus secretion; decreased expression levels of IL-23p19, IL-23R, IL-17A and lactoferrin (LTF); and reduced proportions of Th17 cells in the thymus, spleen, and peripheral blood. Specifically, among the four treatment groups, the anti-IL-23p19 with HY peptide group exhibited the lowest positive production rate of Th17 cells. Our data also showed a significant and positive correlation between CCR5 and IL-23p19 protein expression. These findings suggest that the administration of peptides antagonistic to CCR5 and/or anti-IL-23p19 can reduce airway inflammation in asthmatic mice, most likely through inhibition of the IL-23/Th17 signaling pathway, and the HY peptide can alleviate inflammation not only through the IL-23/Th17 pathway but also through other mechanisms that result in the regulation of inflammation.

show abstract

Host immunogenetics in tick-borne encephalitis virus infection—The CCR5 crossroad

Cited by 16 publications

References 164 publications

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

CCR 5 deficiency impairs CD 4 ⁺ T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis

Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

Contact Info

Product

Resources

About

Host immunogenetics in tick-borne encephalitis virus infection—The CCR5 crossroad

Cited by 16 publications

References 164 publications

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases

CCR 5 deficiency impairs CD 4 + T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis

Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

Contact Info

Product

Resources

About

CCR 5 deficiency impairs CD 4 ⁺ T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis