Extracorporeal membrane oxygenation support improves survival of patients with Hantavirus cardiopulmonary syndrome refractory to medical treatment☆

Wernly, Jorge A.; Dietl, Charles A.; Tabe, Cyril; Pett, Stuart; Crandall, Cameron; Milligan, Karen; Crowley, Mark R.

doi:10.1016/j.ejcts.2011.01.089

Cited by 57 publications

(57 citation statements)

References 16 publications

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“…We demonstrated the feasibility of combining this vaccine with other hantavirus vaccines to expand the breadth of neutralizing activity. Current treatment for hantavirus disease is strictly supportive care [35,36]. But the endemic and episodic emergence of lethal HPS and HFRS warrants the development of a direct countermeasure to prevent disease caused by infection with SNV and other hantaviruses around the world.…”

Section: Discussionmentioning

confidence: 99%

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

Hooper

Josleyn

Ballantyne

et al. 2013

Vaccine

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Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1–15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development.

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Section: Discussionmentioning

confidence: 99%

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

Hooper

Josleyn

Ballantyne

et al. 2013

Vaccine

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“…In the Americas, most HPS infections are caused by the Sin Nombre virus (SNV) or the Andes virus (ANDV), and these infections have resulted in an average fatality rate of 39% (8)(9)(10). Extracorporeal membrane oxygenation support has been shown to improve the survival rates for patients with severe HPS (11,12); however, no HPS-specific vaccines or antivirals currently exist.…”

mentioning

confidence: 99%

Host mTORC1 Signaling Regulates Andes Virus Replication

McNulty

Flint

Nichol

et al. 2013

J Virol

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Hantavirus pulmonary syndrome (HPS) is a severe respiratory disease characterized by pulmonary edema, with fatality rates of 35 to 45%. Disease occurs following infection with pathogenic New World hantaviruses, such as Andes virus (ANDV), which targets lung microvascular endothelial cells. During replication, the virus scavenges 5=-m 7 G caps from cellular mRNA to ensure efficient translation of viral proteins by the host cell cap-dependent translation machinery. In cells, the mammalian target of rapamycin (mTOR) regulates the activity of host cap-dependent translation by integrating amino acid, energy, and oxygen availability signals. Since there is no approved pharmacological treatment for HPS, we investigated whether inhibitors of the mTOR pathway could reduce hantavirus infection. Here, we demonstrate that treatment with the FDA-approved rapamycin analogue temsirolimus (CCI-779) blocks ANDV protein expression and virion release but not entry into primary human microvascular endothelial cells. This effect was specific to viral proteins, as temsirolimus treatment did not block host protein synthesis. We confirmed that temsirolimus targeted host mTOR complex 1 (mTORC1) and not a viral protein, as knockdown of mTORC1 and mTORC1 activators but not mTOR complex 2 components reduced ANDV replication. Additionally, primary fibroblasts from a patient with tuberous sclerosis exhibited increased mTORC1 activity and increased ANDV protein expression, which were blocked following temsirolimus treatment. Finally, we show that ANDV glycoprotein Gn colocalized with mTOR and lysosomes in infected cells. Together, these data demonstrate that mTORC1 signaling regulates ANDV replication and suggest that the hantavirus Gn protein may modulate mTOR and lysosomal signaling during infection, thus bypassing the cellular regulation of translation.

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“…The most common complication of ECMO therapy is a significantly increased bleeding risk due to systemic heparinization, complicated by the clinical picture of thrombocytopenia and platelet dysfunction inherent to HCPS. 11 Given the significant risk for severe hemorrhage resulting in hemodynamic compromise, ECMO is not recommended for all patients. Therefore, a rapid screening method to identify patients who are candidates for ECMO has been developed, including both clinical and peripheral blood smear information.…”

Section: Discussionmentioning

confidence: 99%

Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review

Dvorscak

Czuchlewski

2014

American Journal of Clinical Pathology

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Extracorporeal membrane oxygenation support improves survival of patients with Hantavirus cardiopulmonary syndrome refractory to medical treatment☆

Cited by 57 publications

References 16 publications

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)

Host mTORC1 Signaling Regulates Andes Virus Replication

Successful Triage of Suspected Hantavirus Cardiopulmonary Syndrome by Peripheral Blood Smear Review

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