Timing of CD8 T cell effector responses in viral infections

Stipp, S. L. S.; Iniguez, Abdon; Wan, Frederic Y. M.; Wodarz, Dominik

doi:10.1098/rsos.150661

Cited by 7 publications

(5 citation statements)

References 41 publications

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“…From this pool of epitopes, a total of nine overlapping CTL and TCD4+ epitopes were finally considered as CTL epitopes in our analysis (Table ). Since the cytotoxic T lymphocyte (CTL) plays an important role in the control and clearance of viral infections (Stipp, Iniguez, Wan, & Wodarz, ), those mechanisms driving the evasion of the CTL response could facilitate the perpetuity of the virus into the host. Therefore, we focused on the amino acid changes of the immunogenic E2 protein of the emergent strains in the current study that could induce alterations on the CTL epitopes detected.…”

Section: Resultsmentioning

confidence: 99%

Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: Implication for epidemiological surveillance in endemic areas

Coronado

Rios

Frı́as

et al. 2019

Transbound Emerg Dis

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Classical swine fever (CSF), caused by CSF virus (CSFV), is considered one of the most important infectious diseases with devasting consequences for the pig industry. Recent reports describe the emergence of new CSFV strains resulting from the action of positive selection pressure, due mainly to the bottleneck effect generated by ineffective vaccination. Even though a decrease in the genetic diversity of the positively selected CSFV strains has been observed by several research groups, there is little information about the effect of this selective force on the virulence degree, antigenicity and pathogenicity of this type of strains. Hence, the aim of the current study was to determine the effect of the positive selection pressure on these three parameters of CSFV strains, emerged as result of the bottleneck effects induced by improper vaccination in a CSF‐endemic area. Moreover, the effect of the positively selected strains on the epidemiological surveillance system was assessed. By the combination of in vitro, in vivo and immunoinformatic approaches, we revealed that the action of the positive selection pressure induces a decrease in virulence and alteration in pathogenicity and antigenicity. However, we also noted that the evolutionary process of CSFV, especially in segregated microenvironments, could contribute to the gain‐fitness event, restoring the highly virulent pattern of the circulating strains. Besides, we denoted that the presence of low virulent strains selected by bottleneck effect after inefficient vaccination can lead to a relevant challenge for the epidemiological surveillance of CSF, contributing to under‐reports of the disease, favouring the perpetuation of the virus in the field. In this study, B‐cell and CTL epitopes on the E2 3D‐structure model were also identified. Thus, the current study provides novel and significant insights into variation in virulence, pathogenesis and antigenicity experienced by CSFV strains after the positive selection pressure effect.

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Section: Resultsmentioning

confidence: 99%

Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: Implication for epidemiological surveillance in endemic areas

Coronado

Rios

Frı́as

et al. 2019

Transbound Emerg Dis

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“…After the third BTV challenge, the CD4 + T cell population did not show any significant changes in numbers although at D15 post-third infection (D70pi) CD4 + T cell numbers slightly increased. In general, CD8 + T cell responses peak at about 1 week post-infection in most viral infections, and soon thereafter, virus-specific T cells eliminate the virus [ 24 , 25 ]. Interestingly, CD8 + T cell responses peaked at D14 post-BTV challenge both in acute (D14pi) and secondary responses (D42pi and D70pi) (Figure 3 B).…”

Section: Resultsmentioning

confidence: 99%

Recall T cell responses to bluetongue virus produce a narrowing of the T cell repertoire

Rojas

Rodríguez-Calvo

Sevilla

2017

Vet Res

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In most viral infections, recall T cell responses are critical for protection. The magnitude of these secondary responses can also affect the CD8 and CD4 epitope repertoire diversity. Bluetongue virus (BTV) infection in sheep elicits a T cell response that contributes to viremia control and could be relevant for cross-protection between BTV serotypes. Here, we characterized CD4+ and CD8+ T cell responses during primary and recall responses. During primary immune responses, both CD4+ and CD8+ T cell populations expanded by 14 days post-infection (dpi). CD4+ T cell populations showed a lower peak of expansion and prolonged contraction phase compared to CD8+ T cell populations. Recall responses to BTV challenge led to BTV-specific expansion and activation of CD8+ but not of CD4+ T cells. The evolution of the BTV-specific TCR repertoire was also characterized in response to VP7 peptide stimulation. Striking differences in repertoire development were noted over the time-course of infection. During primary responses, a broader repertoire was induced for MHC-I and MHC-II epitopes. However, during memory responses, a narrowed repertoire was activated towards a dominant motif in VP7 comprising amino acids 139–291. Monocytes were also examined, and expanded during acute infection resolution. In addition, pro-inflammatory cytokine levels increased after BTV inoculation and persisted throughout the experiment, indicative of a prolonged inflammatory state during BTV infections. These findings could have implications for vaccine design as the narrowing memory T cell repertoire induced after BTV re-infection could lead to the development of protective immunodominant TCR repertoires that differs between individual sheep.

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“…challenge was performed during the memory phase, ZIKV-specific CD8 T cells were also recruited to the brain on day 2 post i.c, but at a significantly lower rate, probably due to the limited numbers of circulating ZIKV-specific CD8 T cells at that time point. Additionally, memory CD8 T cells may require some time to acquire effector functions and enter the infected tissue ( 50 , 57 , 58 ). This fits nicely with the observation that by day 5 post i.c, both mice challenged at the expansion phase and in the memory phase, display similar numbers of infiltrating T cells.…”

Section: Discussionmentioning

confidence: 99%

Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers

et al. 2020

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Zika virus (ZIKV), a mosquito-borne flavivirus, came into the spotlight in 2016 when it was found to be associated with an increased rate of microcephalic newborns in Brazil. The virus has further been recognized to cause neurologic complications in children and adults in the form of myelitis, encephalitis, acute disseminated encephalomyelitis (ADEM) and Guillain Barre Syndrome in a fraction of infected individuals. With the ultimate goal of identifying correlates of protection to guide the design of an effective vaccine, the study of the immune response to ZIKV infection has become the focus of research worldwide. Both innate and adaptive immune responses seem to be essential for controlling the infection. Induction of sufficient levels of neutralizing antibodies has been strongly correlated with protection against reinfection in various models, while the role of CD8 T cells as antiviral effectors in the CNS has been controversial. In an attempt to improve our understanding regarding the role of ZIKV-induced CD8 T cells in protective immunity inside the CNS, we have expanded on previous studies in intracranially infected mice. In a recent study, we have demonstrated that, peripheral ZIKV infection in adult C57BL/6 mice induces a robust CD8 T cell response that peaks within a week. In the present study, we used B cell deficient as well as wild-type mice to show that there is a race between CXCR3-dependent recruitment of the effector CD8 T cells and local ZIKV replication, and that CD8 T cells are capable of local viral control if they arrive in the brain early after viral invasion, in appropriate numbers and differentiation state. Our data highlight the benefits of considering this subset when designing vaccines against Zika virus.

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Timing of CD8 T cell effector responses in viral infections

Cited by 7 publications

References 41 publications

Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: Implication for epidemiological surveillance in endemic areas

Positive selection pressure on E2 protein of classical swine fever virus drives variations in virulence, pathogenesis and antigenicity: Implication for epidemiological surveillance in endemic areas

Recall T cell responses to bluetongue virus produce a narrowing of the T cell repertoire

Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers

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