The adaptive immune response does not influence hantavirus disease or persistence in the <scp>S</scp>yrian hamster

Prescott, Joseph; Safronetz, David; Haddock, Elaine; Robertson, Shelly J.; Scott, Dana; Feldmann, Heinz

doi:10.1111/imm.12116

Cited by 44 publications

(55 citation statements)

References 42 publications

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“…On the other hand, depletion of T cells in ANDV-infected Syrian hamsters has no effect on the onset, symptoms, or severity of lethal pulmonary edema, suggesting that T cell responses may not be determinants of the pathogenesis in the hamster model (72,73). A recent study demonstrated that SNV caused a disease such as pulmonary edema in immunosuppressed Syrian hamsters (74).…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

Koma

Yoshimatsu

Nagata

et al. 2014

J Virol

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Hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. However, the pathogenesis of this disease is poorly understood. Here, we demonstrate for the first time that pulmonary vascular permeability is increased by Hantaan virus infection and results in the development of pulmonary edema in C.B-17 severe combined immunodeficiency (SCID) mice lacking functional T cells and B cells. Increases in neutrophils in the lung and blood were observed when pulmonary edema began to be observed in the infected SCID mice. The occurrence of pulmonary edema was inhibited by neutrophil depletion. Moreover, the pulmonary vascular permeability was also significantly suppressed by neutrophil depletion in the infected mice. Taken together, the results suggest that neutrophils play an important role in pulmonary vascular hyperpermeability and the occurrence of pulmonary edema after hantavirus infection in SCID mice. IMPORTANCEAlthough hantavirus infections are characterized by the occurrence of pulmonary edema, the pathogenic mechanism remains largely unknown. In this study, we demonstrated for the first time in vivo that hantavirus infection increases pulmonary vascular permeability and results in the development of pulmonary edema in SCID mice. This novel mouse model for human hantavirus infection will be a valuable tool and will contribute to elucidation of the pathogenetic mechanisms. Although the involvement of neutrophils in the pathogenesis of hantavirus infection has largely been ignored, the results of this study using the mouse model suggest that neutrophils are involved in the vascular hyperpermeability and development of pulmonary edema in hantavirus infection. Further study of the mechanisms could lead to the development of specific treatment for hantavirus infection.

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Section: Discussionmentioning

confidence: 99%

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

Koma

Yoshimatsu

Nagata

et al. 2014

J Virol

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“…we compared the effect of T-cell deletion with that of CD4 þ T-cell deletion in the therapeutic efficacy of oncolytic Ad, by using an anti-mouse CD4 antibody that cross-reacted with T cells of hamsters (19). Compared with deletion of total T cells, deletion of CD4 þ T cells marginally attenuated the antitumor effect of oncolytic Ad, suggesting that the antitumor T-cell response is majorly mediated by CD8 þ T cells (Fig.…”

Section: Antitumor Efficacy Of Oncolytic Ad Depends On T Cells In Hammentioning

confidence: 99%

The Efficacy of Oncolytic Adenovirus Is Mediated by T-cell Responses against Virus and Tumor in Syrian Hamster Model

Wang

et al. 2017

Clinical Cancer Research

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Purpose: Oncolytic adenoviruses (Ad) represent an innovative approach to cancer therapy. Its efficacy depends on multiple actions, including direct tumor lysis and stimulation of antiviral and antitumor immune responses. In this study, we investigated the roles of T-cell responses in oncolytic adenoviral therapy.Experimental Design: An immunocompetent and viral replication-permissive Syrian hamster tumor model was used. The therapeutic mechanisms of oncolytic Ad were investigated by Tcell deletion, immunohistochemical staining, and CTL assay.Results: Deletion of T cells with an anti-CD3 antibody completely demolished the antitumor efficacy of oncolytic Ad. Intratumoral injection of Ad induced strong virus-and tumorspecific T-cell responses, as well as antiviral antibody response.Both antiviral and antitumor T-cell responses contributed to the efficacy of oncolytic Ad. Deletion of T cells increased viral replication and extended the persistence of infectious virus within tumors but almost abrogated the antitumor efficacy. Preexisting antiviral immunity promoted the clearance of injected oncolytic Ad from tumors but had no effect on antitumor efficacy. Strikingly, the repeated treatment with oncolytic Ad has strong therapeutic effect on relapsed tumors or tumors insensitive to the primary viral therapy.Conclusions: These results demonstrate that T cell-mediated immune responses outweigh the direct oncolysis in mediating antitumor efficacy of oncolytic Ad. Our data have a high impact on redesigning the regimen of oncolytic Ad for cancer treatment.

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“…Although the principal target organs of these diseases differ, both infect the endothelium and share many pathologic similarities that lead to fluid loss and electrolyte imbalances, suggesting the underlying disease mechanisms are similar [5,6]. Some evidence suggests a role for the immune response in pathogenesis of hantavirus disease [7,8,9], but a role for lymphocytes is unclear [10,11]. The principal cellular target of hantaviruses are vascular endothelial cells but without conspicuous effects on those cells, although vascular leakage is a prominent feature of hantavirus disease [12].…”

Section: Introductionmentioning

confidence: 99%

Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus)

McGuire

Miedema

Fauver

et al. 2016

Viruses

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Rodent-borne hantaviruses can cause two human diseases with many pathological similarities: hantavirus cardiopulmonary syndrome (HCPS) in the western hemisphere and hemorrhagic fever with renal syndrome in the eastern hemisphere. Each virus is hosted by specific reservoir species without conspicuous disease. HCPS-causing hantaviruses require animal biosafety level-4 (ABSL-4) containment, which substantially limits experimental research of interactions between the viruses and their reservoir hosts. Maporal virus (MAPV) is a South American hantavirus not known to cause disease in humans, thus it can be manipulated under ABSL-3 conditions. The aim of this study was to develop an ABSL-3 hantavirus infection model using the deer mouse (Peromyscus maniculatus), the natural reservoir host of Sin Nombre virus (SNV), and a virus that is pathogenic in another animal model to examine immune response of a reservoir host species. Deer mice were inoculated with MAPV, and viral RNA was detected in several organs of all deer mice during the 56 day experiment. Infected animals generated both nucleocapsid-specific and neutralizing antibodies. Histopathological lesions were minimal to mild with the peak of the lesions detected at 7–14 days postinfection, mainly in the lungs, heart, and liver. Low to modest levels of cytokine gene expression were detected in spleens and lungs of infected deer mice, and deer mouse primary pulmonary cells generated with endothelial cell growth factors were susceptible to MAPV with viral RNA accumulating in the cellular fraction compared to infected Vero cells. Most features resembled that of SNV infection of deer mice, suggesting this model may be an ABSL-3 surrogate for studying the host response of a New World hantavirus reservoir.

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The adaptive immune response does not influence hantavirus disease or persistence in the Syrian hamster

Cited by 44 publications

References 42 publications

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

Neutrophil Depletion Suppresses Pulmonary Vascular Hyperpermeability and Occurrence of Pulmonary Edema Caused by Hantavirus Infection in C.B-17 SCID Mice

The Efficacy of Oncolytic Adenovirus Is Mediated by T-cell Responses against Virus and Tumor in Syrian Hamster Model

Maporal Hantavirus Causes Mild Pathology in Deer Mice (Peromyscus maniculatus)

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