Immune response during hantavirus diseases: implications for immunotherapies and vaccine design

Saavedra, Farides; Díaz, Fabián E.; Retamal-Díaz, Angello; Covián, Camila; González, Pablo A.; Kalergis, Alexis M.

doi:10.1111/imm.13322

Cited by 19 publications

(17 citation statements)

References 157 publications

(427 reference statements)

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“…Therefore, this case report not only enriches the types of virus infection in patients at the late stage of transplantation, but also describes the clinical manifestations and various examination results of such patients after SEOV infection for the first time, shed light on the infection of this virus. It is currently believed that CD8 + T cells, CD4 + T cells, Treg cells, and B cells are involved in the immune response caused by Hantavirus infection [ 11 , 17 ], and serum cytokine expression has also changed [ 17 ]. There are few reports of immunodeficiency patients infected with Hantavirus.…”

Section: Discussionmentioning

confidence: 99%

Central nervous system infection with Seoul Orthohantavirus in a child after hematopoietic stem cell transplantation: a case report

Liu

et al. 2022

Virol J

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Background Patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) are prone to complicate viral infection. Central nervous system (CNS) involvement caused by the viruses is rare but with poor prognosis. Hantavirus, which usually cause hemorrhagic fever with renal syndrome (HFRS), and none case has been reported about these infection in allo-HSCT patients. Case presentation In August 2021, a 13-year-old male child developed intermittent fever and refractory hypotension after allo-HSCT. Magnetic resonance imaging of the head revealed abnormal signal foci in the left midbrain cerebral peduncle and bilateral thalamus. His family reported traces of mouse activity in the patient’s home kitchen. HFRS was suspected, but with no significant kidney damage. The specific immunoglobulin (Ig) G and M of hantavirus were negative. The metagenomic next-generation sequencing (mNGS) detected Seoul Orthohantavirus (SEOV) sequences directly in cerebrospinal fluid and blood. Conclusions Allo-HSCT patients are a high-risk group for infection. Usually the causative agent of infection is difficult to determine, and sometimes the site of infection is concealed. This report highlights the importance of suspecting hantavirus infection in allo-HSCT patients with CNS symptoms despite the absence of renal syndromes. The mNGS is a powerful tool for detecting pathogens. CNS infection with Seoul orthohantavirus in transplant patients is rare but possible as demonstrated in this case. To the best of our knowledge, this is the first reported case employing mNGS to diagnose SEOV caused CNS infection in an allo-HSCT patient.

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Section: Discussionmentioning

confidence: 99%

Central nervous system infection with Seoul Orthohantavirus in a child after hematopoietic stem cell transplantation: a case report

Liu

et al. 2022

Virol J

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“…It should be pointed out that genetic factors could contribute to age dependent differences in NE severity. Genetic mechanisms have been suggested also to play role in cytokine storms, the leading factor in pathogenesis of hantavirus infection [25,49,50]. Recent studies of genetic factors have implicated several IL6 gene variations in pathogenesis of coronavirus infection 2019 (COVID-19) [51], a disease where severity has a strong association with the likelihood of a cytokine storm [52].…”

Section: Discussionmentioning

confidence: 99%

Serum Cytokine Alterations Associated with Age of Patients with Nephropathia Epidemica

Shakirova

Khaertynova

Markelova

et al. 2022

BioMed Research International

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Nephropathia epidemica (NE) is a zoonotic disease caused by hantaviruses transmitted from rodents, endemic in the Republic of Tatarstan, Russia. The disease presents clinically with mild, moderate, and severe forms, and time-dependent febrile, oliguric, and polyuric stages of the disease are also recognized. The patient’s cytokine responses have been suggested to play a central role in disease pathogenesis; however, little is known about the different patterns of cytokine expression in NE in cohorts of different ages and sexes. Serum samples and clinical records were collected from 139 patients and 57 controls (healthy donors) and were used to analyze 48 analytes with the Bio-Plex multiplex magnetic bead-based antibody detection kits. Principal component analysis of 137 patient and 55 controls (for which there was full data) identified two components that individually accounted for >15% of the total variance in results and together for 38% of the total variance. PC1 represented a proinflammatory TH17/TH2 cell antiviral cytokine profile and PC2 a more antiviral cytokine profile with patients tending to display one or the other of these. Severity of disease and stage of illness did not show any correlation with PC1 profiles; however, significant differences were seen in patients with high PC1 profiles vs. lower for a number of individual clinical parameters: High PC1 patients showed a reduced number of febrile days, but higher maximum urine output, higher creatinine levels, and lower platelet levels. Overall, the results of this study point towards a stronger proinflammatory profile occurring in younger NE patients, this being associated with markers of acute kidney injury and low levels of high-density cholesterol. This is consistent with previous work indicating that the pathology of NE is immune driven, with an inflammatory immune response being associated with disease and that this immune response is more extreme in younger patients.

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“…Hantavirus pathogenesis can be explained by the "cytokine storm" hypothesis, where clinical symptoms are the result of overproduction of proinflammatory cytokines [22,50,51]. Therefore, we sought to determine whether expression of serum cytokines in patients with NE differed between regions of the RT and the RM.…”

Section: Discussionmentioning

confidence: 99%

Cytokine, Chemokine, and Metalloprotease Activation in the Serum of Patients with Nephropathia Epidemica from the Republic of Tatarstan and the Republic of Mordovia, Russia

et al. 2021

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Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic of Tatarstan (RT) and the Republic of Mordovia (RM), is a mild form of hemorrhagic fever with renal syndrome caused by infection with rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little is known about the hantavirus strains associated with human infection in these regions. There is also limited understanding of the pathogenesis of NE in the RT and the RM. To address these knowledge gaps, we conducted comparative analyses of patients with NE in the RT and the RM. Clinical symptoms were more severe in patients with NE from the RM with longer observed duration of fever symptoms and hospitalization. Analysis of patient sera showed changes in the levels of numerous cytokines, chemokines, and matrix metalloproteases (MMPs) in patients with NE from both the RT and the RM, suggesting leukocyte activation, extracellular matrix degradation, and leukocyte chemotaxis. Interestingly, levels of several cytokines were distinctly different between patients NE from the RT when compared with those from the RM. These differences were not related to the genetic variation of orthohantaviruses circulating in those regions, as sequence analysis showed that Puumala virus (PUUV) was the causative agent of NE in these regions. Additionally, only the “Russia” (RUS) genetic lineage of PUUV was detected in the serum samples of patients with NE from both the RT and the RM. We therefore conclude that differences in serum cytokine, chemokine, and MMP levels between the RT and the RM are related to environmental factors and lifestyle differences that influence individual immune responses to orthohantavirus infection.

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Immune response during hantavirus diseases: implications for immunotherapies and vaccine design

Cited by 19 publications

References 157 publications

Central nervous system infection with Seoul Orthohantavirus in a child after hematopoietic stem cell transplantation: a case report

Central nervous system infection with Seoul Orthohantavirus in a child after hematopoietic stem cell transplantation: a case report

Serum Cytokine Alterations Associated with Age of Patients with Nephropathia Epidemica

Cytokine, Chemokine, and Metalloprotease Activation in the Serum of Patients with Nephropathia Epidemica from the Republic of Tatarstan and the Republic of Mordovia, Russia

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