scholarly journals Host response: Cross-fit T cells battle Zika virus

2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Matthew Collins ◽  
Aravinda de Silva
Keyword(s):  
T Cells ◽  
2021 ◽  
Author(s):  
Blake Schouest ◽  
Alba Grifoni ◽  
John Pham ◽  
Jose Mateus ◽  
John Sydney ◽  
...  

The mosquito-borne Zika virus (ZIKV) spread rapidly into regions where dengue virus (DENV) is endemic, and flavivirus cross-reactive T cell responses have been observed repeatedly in animal models and in humans. Pre-existing cellular immunity to DENV is thought to contribute to protection in subsequent ZIKV infection, but the epitope targets of cross-reactive T cell responses have not been comprehensively identified. Using human blood samples from the DENV-endemic regions of Nicaragua and Sri Lanka that were collected before the global spread of ZIKV in 2016, we employed an in vitro expansion strategy to map ZIKV T cell epitopes in ZIKV-unexposed, DENV-seropositive donors. We identified 93 epitopes across the ZIKV proteome, and we observed patterns of immunodominance that were dependent on antigen size and sequence identity to DENV. We confirmed the immunogenicity of these epitopes through a computational HLA binding analysis, and we showed that cross-reactive T cells specifically recognize ZIKV peptides homologous to DENV sequences. We also found that these CD4 responses were derived from the memory T cell compartment. These data have implications for understanding the dynamics of flavivirus-specific T cell immunity in endemic areas. Importance Multiple flaviviruses, including Zika (ZIKV) and the four serotypes of dengue (DENV) viruses, are prevalent in the same large tropical and equatorial areas inhabited by hundreds of millions of people. The interplay of DENV and ZIKV infection is especially relevant, as these two viruses are endemic in largely overlapping regions, have significant sequence similarity, and share the same arthropod vector. Here, we define the targets of pre-existing immunity to ZIKV in unexposed subjects collected in dengue-endemic areas. We demonstrate that pre-existing immunity to DENV could shape ZIKV-specific responses, and DENV-ZIKV cross-reactive T cells can be expanded by stimulation with ZIKV peptides. The issue of potential ZIKV and DENV cross-reactivity is of relevance for understanding patterns of natural immunity, as well as for the development of diagnostic tests and vaccines.


Cell Reports ◽  
2020 ◽  
Vol 31 (4) ◽  
pp. 107566 ◽  
Author(s):  
Jinsheng Wen ◽  
Ying-Ting Wang ◽  
Kristen M. Valentine ◽  
Rúbens Prince dos Santos Alves ◽  
Zhigang Xu ◽  
...  

2019 ◽  
Vol 25 (3) ◽  
pp. S348-S349
Author(s):  
Ryo Hanajiri ◽  
Michael D. Keller ◽  
Gelina M. Sani ◽  
Patrick J. Hanley ◽  
Esper G. Kallas ◽  
...  

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Hana M El Sahly ◽  
Rodion Gorchakov ◽  
Lilin Lai ◽  
Muktha S Natrajan ◽  
Shital M Patel ◽  
...  

Abstract Background Clinical, virologic, and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods US subjects with suspected ZIKV infection were enrolled. Clinical data and specimens were prospectively collected for ZIKV RNA detection and serologic and cellular assays. Confirmed ZIKV infection (cases) and ZIKV-negative (controls) subjects were compared. Dengue-experienced and dengue-naïve cases were also compared. Results We enrolled 45 cases and 14 controls. Commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%), and arthralgia (82.2% and 54.5%), respectively. The sensitivity (94%) and duration of infection detection (80% positivity at 65–79 days after disease onset) by polymerase chain reaction were highest in whole-blood specimens. ZIKV-neutralizing antibodies had a half-life of 105 days and were significantly higher in dengue virus–experienced cases than naïve ones (P = .046). In intracellular cytokine staining assays, the ZIKV proteins targeted most often by peripheral blood mononuclear cells from cases were structural proteins C and E for CD4+ T cells and nonstructural proteins NS3, NS5, and NS4B for CD8+ T cells. Conclusions ZIKV RNA detection was more frequent and prolonged in whole-blood specimens. Immunoglobulin G (IgG) and neutralizing antibodies, but not IgM, were influenced by prior dengue infection. Robust cellular responses to E and nonstructural proteins have potential vaccine development implications.


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 820 ◽  
Author(s):  
Ryan D. Pardy ◽  
Martin J. Richer

CD4 and CD8 T cells are an important part of the host’s capacity to defend itself against viral infections. During flavivirus infections, T cells have been implicated in both protective and pathogenic responses. Given the recent emergence of Zika virus (ZIKV) as a prominent global health threat, the question remains as to how T cells contribute to anti-ZIKV immunity. Furthermore, high homology between ZIKV and other, co-circulating flaviviruses opens the possibility of positive or negative effects of cross-reactivity due to pre-existing immunity. In this review, we will discuss the CD4 and CD8 T cell responses to ZIKV, and the lessons we have learned from both mouse and human infections. In addition, we will consider the possibility of whether T cells, in the context of flavivirus-naïve and flavivirus-immune subjects, play a role in promoting ZIKV pathogenesis during infection.


2019 ◽  
Vol 15 (1) ◽  
pp. e1007474 ◽  
Author(s):  
Annie Elong Ngono ◽  
Matthew P. Young ◽  
Maximilian Bunz ◽  
Zhigang Xu ◽  
Sararat Hattakam ◽  
...  

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Carolina V. Messias ◽  
Julia P. Lemos ◽  
Daniela P. Cunha ◽  
Zilton Vasconcelos ◽  
Lidiane M. S. Raphael ◽  
...  

Abstract Background Zika virus (ZIKV) infection gained public health concern after the 2015 outbreak in Brazil, when microcephaly rates increased in babies born from infected mothers. It was demonstrated that ZIKV causes a congenital Zika virus syndrome, including various alterations in the development of the central nervous system. Although the infection of cells from the nervous system has been well documented, less is known in respect of ZIKV ability to infect immune cells. Herein, we investigated if peripheral blood mononuclear cells (PBMCs), freshly-isolated from healthy donors, could be infected by ZIKV. Methods PBMCs from healthy donors were isolated and cultured in medium with ZIKV strain Rio-U1 (MOI = 0.1). Infection was analyzed by RT-qPCR and flow cytometry. Results We detected the ZIKV RNA in PBMCs from all donors by RT-qPCR analysis. The detection of viral antigens by flow cytometry revealed that PBMC from more than 50% the donors were infected by ZIKV, with CD3+CD4+ T cells, CD3−CD19+ B cells and CD3+CD8+ T cells being, respectively, the most frequently infected subpopulations, followed by CD14+ monocytes. Additionally, we observed high variability in PBMC infection rates among different donors, either by numbers or type infected cells. Conclusions These findings raise the hypothesis that PBMCs can act as a reservoir of the virus, which may facilitate viral dissemination to different organs, including immune-privileged sites.


2020 ◽  
Vol 217 (9) ◽  
Author(s):  
Dong Chen ◽  
Zhiliang Duan ◽  
Wenhua Zhou ◽  
Weiwei Zou ◽  
Shengwei Jin ◽  
...  

Cross-reactive anti-flaviviral immunity can influence the outcome of infections with heterologous flaviviruses. However, it is unclear how the interplay between cross-reactive antibodies and T cells tilts the balance toward pathogenesis versus protection during secondary Zika virus (ZIKV) and Japanese encephalitis virus (JEV) infections. We show that sera and IgG from JEV-vaccinated humans and JEV-inoculated mice cross-reacted with ZIKV, exacerbated lethal ZIKV infection upon transfer to mice, and promoted viral replication and mortality upon ZIKV infection of the neonates born to immune mothers. In contrast, transfer of CD8+ T cells from JEV-exposed mice was protective, reducing the viral burden and mortality of ZIKV-infected mice and abrogating the lethal effects of antibody-mediated enhancement of ZIKV infection in mice. Conversely, cross-reactive anti-ZIKV antibodies or CD8+ T cells displayed the same pathogenic or protective effects upon JEV infection, with the exception that maternally acquired anti-ZIKV antibodies had no effect on JEV infection of the neonates. These results provide clues for developing safe anti-JEV/ZIKV vaccines.


Stress ◽  
2012 ◽  
Vol 15 (6) ◽  
pp. 637-646 ◽  
Author(s):  
Jay Campisi ◽  
Craig Sharkey ◽  
John D. Johnson ◽  
Alexzander Asea ◽  
Thomas Maslanik ◽  
...  

2010 ◽  
Vol 78 (4) ◽  
pp. 1670-1681 ◽  
Author(s):  
Yin Wang ◽  
Uma Nagarajan ◽  
Leah Hennings ◽  
Anne K. Bowlin ◽  
Roger G. Rank

ABSTRACT Very little is known about the host response to chlamydial genital infection in the male, particularly about the nature of the local response in the urethra. In this study, the pathological and immunologic responses to urethral infection of the male guinea pig with Chlamydia caviae (Chlamydophila caviae) were characterized both during a primary infection and following a challenge infection. A dose-response experiment found that the 50% infectious dose for male urethral infection was 78 inclusion-forming units. The histopathologic response was similar to that of the female, with an initial acute inflammatory response followed by a chronic inflammatory response and plasma cell infiltration. Production of IgG and IgA antibodies in local urethral secretions developed following infection, and levels of both increased in a typical anamnestic response following a challenge infection. CD4 and CD8 T cells, as well as B cells, were observed in the local site by flow cytometry, with a slightly increased number of CD8 cells. Following challenge infection, the dominant anamnestic response was solely in the B-cell compartment, with only a minimal number of T cells. The T-cell response was clearly a Th1 response, as judged by increased levels of gamma interferon (IFN-γ), interleukin-12 p40 (IL-12p40), and IL-2. The proinflammatory cytokines and chemokines IL-8, IL-1β, tumor necrosis factor alpha (TNF-α), CCL2 (monocyte chemoattractant protein 1 [MCP-1]), and CCL5 (RANTES) were elicited in the urethra following primary infection, but only CCL5 showed increased levels upon challenge. This study represents the first comprehensive analysis of the local immune response in the male urethra to a chlamydial genital infection.


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