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1. Virology under the Microscope-a Call for Rational Discourse.

Author

Goodrum, Felicia, Goodrum, Felicia, Lowen, Anice C, Lakdawala, Seema, Alwine, James, Casadevall, Arturo, Imperiale, Michael J, Atwood, Walter, Avgousti, Daphne, Baines, Joel, Banfield, Bruce, Banks, Lawrence, Bhaduri-McIntosh, Sumita, Bhattacharya, Deepta, Blanco-Melo, Daniel, Bloom, David, Boon, Adrianus, Boulant, Steeve, Brandt, Curtis, Broadbent, Andrew, Brooke, Christopher, Cameron, Craig, Campos, Samuel, Caposio, Patrizia, Chan, Gary, Cliffe, Anna, Coffin, John, Collins, Kathleen, Damania, Blossom, Daugherty, Matthew, Debbink, Kari, DeCaprio, James, Dermody, Terence, Dikeakos, Jimmy, DiMaio, Daniel, Dinglasan, Rhoel, Duprex, W Paul, Dutch, Rebecca, Elde, Nels, Emerman, Michael, Enquist, Lynn, Fane, Bentley, Fernandez-Sesma, Ana, Flenniken, Michelle, Frappier, Lori, Frieman, Matthew, Frueh, Klaus, Gack, Michaela, Gaglia, Marta, Gallagher, Tom, Galloway, Denise, García-Sastre, Adolfo, Geballe, Adam, Glaunsinger, Britt, Goff, Stephen, Greninger, Alexander, Hancock, Meaghan, Harris, Eva, Heaton, Nicholas, Heise, Mark, Heldwein, Ekaterina, Hogue, Brenda, Horner, Stacy, Hutchinson, Edward, Hyser, Joseph, Jackson, William, Kalejta, Robert, Kamil, Jeremy, Karst, Stephanie, Kirchhoff, Frank, Knipe, David, Kowalik, Timothy, Lagunoff, Michael, Laimins, Laimonis, Langlois, Ryan, Lauring, Adam, Lee, Benhur, Leib, David, Liu, Shan-Lu, Longnecker, Richard, Lopez, Carolina, Luftig, Micah, Lund, Jennifer, Manicassamy, Balaji, McFadden, Grant, McIntosh, Michael, Mehle, Andrew, Miller, W Allen, Mohr, Ian, Moody, Cary, Moorman, Nathaniel, Moscona, Anne, Mounce, Bryan, Munger, Joshua, Münger, Karl, Murphy, Eain, Naghavi, Mojgan, Nelson, Jay, Neufeldt, Christopher, Nikolich, Janko, O'Connor, Christine, Goodrum, Felicia, Goodrum, Felicia, Lowen, Anice C, Lakdawala, Seema, Alwine, James, Casadevall, Arturo, Imperiale, Michael J, Atwood, Walter, Avgousti, Daphne, Baines, Joel, Banfield, Bruce, Banks, Lawrence, Bhaduri-McIntosh, Sumita, Bhattacharya, Deepta, Blanco-Melo, Daniel, Bloom, David, Boon, Adrianus, Boulant, Steeve, Brandt, Curtis, Broadbent, Andrew, Brooke, Christopher, Cameron, Craig, Campos, Samuel, Caposio, Patrizia, Chan, Gary, Cliffe, Anna, Coffin, John, Collins, Kathleen, Damania, Blossom, Daugherty, Matthew, Debbink, Kari, DeCaprio, James, Dermody, Terence, Dikeakos, Jimmy, DiMaio, Daniel, Dinglasan, Rhoel, Duprex, W Paul, Dutch, Rebecca, Elde, Nels, Emerman, Michael, Enquist, Lynn, Fane, Bentley, Fernandez-Sesma, Ana, Flenniken, Michelle, Frappier, Lori, Frieman, Matthew, Frueh, Klaus, Gack, Michaela, Gaglia, Marta, Gallagher, Tom, Galloway, Denise, García-Sastre, Adolfo, Geballe, Adam, Glaunsinger, Britt, Goff, Stephen, Greninger, Alexander, Hancock, Meaghan, Harris, Eva, Heaton, Nicholas, Heise, Mark, Heldwein, Ekaterina, Hogue, Brenda, Horner, Stacy, Hutchinson, Edward, Hyser, Joseph, Jackson, William, Kalejta, Robert, Kamil, Jeremy, Karst, Stephanie, Kirchhoff, Frank, Knipe, David, Kowalik, Timothy, Lagunoff, Michael, Laimins, Laimonis, Langlois, Ryan, Lauring, Adam, Lee, Benhur, Leib, David, Liu, Shan-Lu, Longnecker, Richard, Lopez, Carolina, Luftig, Micah, Lund, Jennifer, Manicassamy, Balaji, McFadden, Grant, McIntosh, Michael, Mehle, Andrew, Miller, W Allen, Mohr, Ian, Moody, Cary, Moorman, Nathaniel, Moscona, Anne, Mounce, Bryan, Munger, Joshua, Münger, Karl, Murphy, Eain, Naghavi, Mojgan, Nelson, Jay, Neufeldt, Christopher, Nikolich, Janko, and O'Connor, Christine

Abstract

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Published
2023

2. Virology under the Microscope-a Call for Rational Discourse.

Author

Goodrum, Felicia, Goodrum, Felicia, Lowen, Anice C, Lakdawala, Seema, Alwine, James, Casadevall, Arturo, Imperiale, Michael J, Atwood, Walter, Avgousti, Daphne, Baines, Joel, Banfield, Bruce, Banks, Lawrence, Bhaduri-McIntosh, Sumita, Bhattacharya, Deepta, Blanco-Melo, Daniel, Bloom, David, Boon, Adrianus, Boulant, Steeve, Brandt, Curtis, Broadbent, Andrew, Brooke, Christopher, Cameron, Craig, Campos, Samuel, Caposio, Patrizia, Chan, Gary, Cliffe, Anna, Coffin, John, Collins, Kathleen, Damania, Blossom, Daugherty, Matthew, Debbink, Kari, DeCaprio, James, Dermody, Terence, Dikeakos, Jimmy, DiMaio, Daniel, Dinglasan, Rhoel, Duprex, W Paul, Dutch, Rebecca, Elde, Nels, Emerman, Michael, Enquist, Lynn, Fane, Bentley, Fernandez-Sesma, Ana, Flenniken, Michelle, Frappier, Lori, Frieman, Matthew, Frueh, Klaus, Gack, Michaela, Gaglia, Marta, Gallagher, Tom, Galloway, Denise, García-Sastre, Adolfo, Geballe, Adam, Glaunsinger, Britt, Goff, Stephen, Greninger, Alexander, Hancock, Meaghan, Harris, Eva, Heaton, Nicholas, Heise, Mark, Heldwein, Ekaterina, Hogue, Brenda, Horner, Stacy, Hutchinson, Edward, Hyser, Joseph, Jackson, William, Kalejta, Robert, Kamil, Jeremy, Karst, Stephanie, Kirchhoff, Frank, Knipe, David, Kowalik, Timothy, Lagunoff, Michael, Laimins, Laimonis, Langlois, Ryan, Lauring, Adam, Lee, Benhur, Leib, David, Liu, Shan-Lu, Longnecker, Richard, Lopez, Carolina, Luftig, Micah, Lund, Jennifer, Manicassamy, Balaji, McFadden, Grant, McIntosh, Michael, Mehle, Andrew, Miller, W Allen, Mohr, Ian, Moody, Cary, Moorman, Nathaniel, Moscona, Anne, Mounce, Bryan, Munger, Joshua, Münger, Karl, Murphy, Eain, Naghavi, Mojgan, Nelson, Jay, Neufeldt, Christopher, Nikolich, Janko, O'Connor, Christine, Goodrum, Felicia, Goodrum, Felicia, Lowen, Anice C, Lakdawala, Seema, Alwine, James, Casadevall, Arturo, Imperiale, Michael J, Atwood, Walter, Avgousti, Daphne, Baines, Joel, Banfield, Bruce, Banks, Lawrence, Bhaduri-McIntosh, Sumita, Bhattacharya, Deepta, Blanco-Melo, Daniel, Bloom, David, Boon, Adrianus, Boulant, Steeve, Brandt, Curtis, Broadbent, Andrew, Brooke, Christopher, Cameron, Craig, Campos, Samuel, Caposio, Patrizia, Chan, Gary, Cliffe, Anna, Coffin, John, Collins, Kathleen, Damania, Blossom, Daugherty, Matthew, Debbink, Kari, DeCaprio, James, Dermody, Terence, Dikeakos, Jimmy, DiMaio, Daniel, Dinglasan, Rhoel, Duprex, W Paul, Dutch, Rebecca, Elde, Nels, Emerman, Michael, Enquist, Lynn, Fane, Bentley, Fernandez-Sesma, Ana, Flenniken, Michelle, Frappier, Lori, Frieman, Matthew, Frueh, Klaus, Gack, Michaela, Gaglia, Marta, Gallagher, Tom, Galloway, Denise, García-Sastre, Adolfo, Geballe, Adam, Glaunsinger, Britt, Goff, Stephen, Greninger, Alexander, Hancock, Meaghan, Harris, Eva, Heaton, Nicholas, Heise, Mark, Heldwein, Ekaterina, Hogue, Brenda, Horner, Stacy, Hutchinson, Edward, Hyser, Joseph, Jackson, William, Kalejta, Robert, Kamil, Jeremy, Karst, Stephanie, Kirchhoff, Frank, Knipe, David, Kowalik, Timothy, Lagunoff, Michael, Laimins, Laimonis, Langlois, Ryan, Lauring, Adam, Lee, Benhur, Leib, David, Liu, Shan-Lu, Longnecker, Richard, Lopez, Carolina, Luftig, Micah, Lund, Jennifer, Manicassamy, Balaji, McFadden, Grant, McIntosh, Michael, Mehle, Andrew, Miller, W Allen, Mohr, Ian, Moody, Cary, Moorman, Nathaniel, Moscona, Anne, Mounce, Bryan, Munger, Joshua, Münger, Karl, Murphy, Eain, Naghavi, Mojgan, Nelson, Jay, Neufeldt, Christopher, Nikolich, Janko, and O'Connor, Christine

Abstract

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Published
2023

3. Virology under the Microscope-a Call for Rational Discourse.

Author

Goodrum, Felicia, Goodrum, Felicia, Lowen, Anice C, Lakdawala, Seema, Alwine, James, Casadevall, Arturo, Imperiale, Michael J, Atwood, Walter, Avgousti, Daphne, Baines, Joel, Banfield, Bruce, Banks, Lawrence, Bhaduri-McIntosh, Sumita, Bhattacharya, Deepta, Blanco-Melo, Daniel, Bloom, David, Boon, Adrianus, Boulant, Steeve, Brandt, Curtis, Broadbent, Andrew, Brooke, Christopher, Cameron, Craig, Campos, Samuel, Caposio, Patrizia, Chan, Gary, Cliffe, Anna, Coffin, John, Collins, Kathleen, Damania, Blossom, Daugherty, Matthew, Debbink, Kari, DeCaprio, James, Dermody, Terence, Dikeakos, Jimmy, DiMaio, Daniel, Dinglasan, Rhoel, Duprex, W Paul, Dutch, Rebecca, Elde, Nels, Emerman, Michael, Enquist, Lynn, Fane, Bentley, Fernandez-Sesma, Ana, Flenniken, Michelle, Frappier, Lori, Frieman, Matthew, Frueh, Klaus, Gack, Michaela, Gaglia, Marta, Gallagher, Tom, Galloway, Denise, García-Sastre, Adolfo, Geballe, Adam, Glaunsinger, Britt, Goff, Stephen, Greninger, Alexander, Hancock, Meaghan, Harris, Eva, Heaton, Nicholas, Heise, Mark, Heldwein, Ekaterina, Hogue, Brenda, Horner, Stacy, Hutchinson, Edward, Hyser, Joseph, Jackson, William, Kalejta, Robert, Kamil, Jeremy, Karst, Stephanie, Kirchhoff, Frank, Knipe, David, Kowalik, Timothy, Lagunoff, Michael, Laimins, Laimonis, Langlois, Ryan, Lauring, Adam, Lee, Benhur, Leib, David, Liu, Shan-Lu, Longnecker, Richard, Lopez, Carolina, Luftig, Micah, Lund, Jennifer, Manicassamy, Balaji, McFadden, Grant, McIntosh, Michael, Mehle, Andrew, Miller, W Allen, Mohr, Ian, Moody, Cary, Moorman, Nathaniel, Moscona, Anne, Mounce, Bryan, Munger, Joshua, Münger, Karl, Murphy, Eain, Naghavi, Mojgan, Nelson, Jay, Neufeldt, Christopher, Nikolich, Janko, O'Connor, Christine, Goodrum, Felicia, Goodrum, Felicia, Lowen, Anice C, Lakdawala, Seema, Alwine, James, Casadevall, Arturo, Imperiale, Michael J, Atwood, Walter, Avgousti, Daphne, Baines, Joel, Banfield, Bruce, Banks, Lawrence, Bhaduri-McIntosh, Sumita, Bhattacharya, Deepta, Blanco-Melo, Daniel, Bloom, David, Boon, Adrianus, Boulant, Steeve, Brandt, Curtis, Broadbent, Andrew, Brooke, Christopher, Cameron, Craig, Campos, Samuel, Caposio, Patrizia, Chan, Gary, Cliffe, Anna, Coffin, John, Collins, Kathleen, Damania, Blossom, Daugherty, Matthew, Debbink, Kari, DeCaprio, James, Dermody, Terence, Dikeakos, Jimmy, DiMaio, Daniel, Dinglasan, Rhoel, Duprex, W Paul, Dutch, Rebecca, Elde, Nels, Emerman, Michael, Enquist, Lynn, Fane, Bentley, Fernandez-Sesma, Ana, Flenniken, Michelle, Frappier, Lori, Frieman, Matthew, Frueh, Klaus, Gack, Michaela, Gaglia, Marta, Gallagher, Tom, Galloway, Denise, García-Sastre, Adolfo, Geballe, Adam, Glaunsinger, Britt, Goff, Stephen, Greninger, Alexander, Hancock, Meaghan, Harris, Eva, Heaton, Nicholas, Heise, Mark, Heldwein, Ekaterina, Hogue, Brenda, Horner, Stacy, Hutchinson, Edward, Hyser, Joseph, Jackson, William, Kalejta, Robert, Kamil, Jeremy, Karst, Stephanie, Kirchhoff, Frank, Knipe, David, Kowalik, Timothy, Lagunoff, Michael, Laimins, Laimonis, Langlois, Ryan, Lauring, Adam, Lee, Benhur, Leib, David, Liu, Shan-Lu, Longnecker, Richard, Lopez, Carolina, Luftig, Micah, Lund, Jennifer, Manicassamy, Balaji, McFadden, Grant, McIntosh, Michael, Mehle, Andrew, Miller, W Allen, Mohr, Ian, Moody, Cary, Moorman, Nathaniel, Moscona, Anne, Mounce, Bryan, Munger, Joshua, Münger, Karl, Murphy, Eain, Naghavi, Mojgan, Nelson, Jay, Neufeldt, Christopher, Nikolich, Janko, and O'Connor, Christine

Abstract

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we - a broad group of working virologists - seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology.

Published
2023

4. Potency of Fusion-Inhibitory Lipopeptides against SARS-CoV-2 Variants of Concern

Author

Schmitz, Katharina S., Geers, Daryl, de Vries, Rory D., Bovier, T. Francesca, Mykytyn, Anna Z., Geurts van Kessel, Corine H., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., Moscona, Anne, Schmitz, Katharina S., Geers, Daryl, de Vries, Rory D., Bovier, T. Francesca, Mykytyn, Anna Z., Geurts van Kessel, Corine H., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., and Moscona, Anne

Abstract

The ability of SARS-CoV-2 to evolve in response to selective pressures poses a challenge to vaccine and antiviral efficacy. The S1 subunit of the spike (S) protein contains the receptor-binding domain and is therefore under selective pressure to evade neutralizing antibodies elicited by vaccination or infection. In contrast, the S2 subunit of S is only transiently exposed after receptor binding, which makes it a less efficient target for antibodies. As a result, S2 has a lower mutational frequency than S1. We recently described monomeric and dimeric SARS-CoV-2 fusion-inhibitory lipopeptides that block viral infection by interfering with S2 conformational rearrangements during viral entry. Importantly, a dimeric lipopeptide was shown to block SARS-CoV-2 transmission between ferrets in vivo. Because the S2 subunit is relatively conserved in newly emerging SARS-CoV-2 variants of concern (VOCs), we hypothesize that fusion-inhibitory lipopeptides are cross-protective against infection with VOCs. Here, we directly compared the in vitro efficacies of two fusion-inhibitory lipopeptides against VOC, in comparison with a set of seven postvaccination sera (two doses) and a commercial monoclonal antibody preparation. For the beta, delta, and omicron VOCs, it has been reported that convalescent and postvaccination sera are less potent in virus neutralization assays. Both fusion-inhibitory lipopeptides were equally effective against all five VOCs compared to ancestral virus, whereas postvaccination sera and therapeutic monoclonal antibody lost potency to newer VOCs, in particular to omicron BA.1 and BA.2. The neutralizing activity of the lipopeptides is consistent, and they can be expected to neutralize future VOCs based on their mechanism of action.

Published
2022

5. Repurposing an In Vitro Measles Virus Dissemination Assay for Screening of Antiviral Compounds

Author

Schmitz, Katharina S., Lange, Mona V., Gommers, Lennert, Handrejk, Kim, Porter, Danielle P., Alabi, Christopher A., Moscona, Anne, Porotto, Matteo, de Vries, Rory D., de Swart, Rik L., Schmitz, Katharina S., Lange, Mona V., Gommers, Lennert, Handrejk, Kim, Porter, Danielle P., Alabi, Christopher A., Moscona, Anne, Porotto, Matteo, de Vries, Rory D., and de Swart, Rik L.

Abstract

Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks.

Published
2022

6. Modeling Infection and Tropism of Human Parainfluenza Virus Type 3 in Ferrets

Author

Rijsbergen, Laurine C., Schmitz, Katharina S., Begeman, Lineke, Drew-Bear, Jennifer, Gommers, Lennert, Lamers, Mart M., Greninger, Alexander L., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., Moscona, Anne, de Vries, Rory D., Rijsbergen, Laurine C., Schmitz, Katharina S., Begeman, Lineke, Drew-Bear, Jennifer, Gommers, Lennert, Lamers, Mart M., Greninger, Alexander L., Haagmans, Bart L., Porotto, Matteo, de Swart, Rik L., Moscona, Anne, and de Vries, Rory D.

Abstract

Human parainfluenza virus type 3 (HPIV-3) is a significant cause of lower respiratory tract infections, with the most severe disease in young infants, immunocompromised individuals, and the elderly. HPIV-3 infections are currently untreatable with licensed therapeutics, and prophylactic and therapeutic options are needed for patients at risk. To complement existing human airway models of HPIV-3 infection and develop an animal model to assess novel intervention strategies, we evaluated infection and transmission of HPIV-3 in ferrets. A well-characterized human clinical isolate (CI) of HPIV-3 engineered to express enhanced green fluorescent protein (rHPIV-3 CI-1-EGFP) was passaged on primary human airway epithelial cells (HAE) or airway organoids (AO) to avoid tissue culture adaptations. rHPIV3 CI-1-EGFP infection was assessed in vitro in ferret AO and in ferrets in vivo. Undifferentiated and differentiated ferret AO cultures supported rHPIV-3 CI-1-EGFP replication, but the ferret primary airway cells from AO were less susceptible and permissive than HAE. In vivo rHPIV-3 CI-1-EGFP replicated in the upper and lower airways of ferrets and targeted respiratory epithelial cells, olfactory epithelial cells, type I pneumocytes, and type II pneumocytes. The infection efficiently induced specific antibody responses. Taken together, ferrets are naturally susceptible to HPIV-3 infection; however, limited replication was observed that led to neither overt clinical signs nor ferret-to-ferret transmission. However, in combination with ferret AO, the ferret model of HPIV-3 infection, tissue tropism, and neutralizing antibodies complements human ex vivo lung models and can be used as a platform for prevention and treatment studies for this important respiratory pathogen. IMPORTANCE HPIV-3 is an important cause of pediatric disease and significantly impacts the elderly. Increasing numbers of immunocompromised patients suffer from HPIV-3 infections, often related to problems with v

Published
2022

7. Absence of COVID-19-associated changes in plasma coagulation proteins and pulmonary thrombosis in the ferret model

Author

Kreft, Iris C., Winiarczyk, Roy R.A., Tanis, Fric J., van der Zwaan, Carmen, Schmitz, Katharina S., Hoogendijk, Arie J., de Swart, Rik L., Moscona, Anne, Porotto, Matteo, Salvatori, Daniela C.F., de Vries, Rory D., de Maat, Moniek P.M., van den Biggelaar, Maartje, van Vlijmen, Bart J.M., Kreft, Iris C., Winiarczyk, Roy R.A., Tanis, Fric J., van der Zwaan, Carmen, Schmitz, Katharina S., Hoogendijk, Arie J., de Swart, Rik L., Moscona, Anne, Porotto, Matteo, Salvatori, Daniela C.F., de Vries, Rory D., de Maat, Moniek P.M., van den Biggelaar, Maartje, and van Vlijmen, Bart J.M.

Abstract

Background: Many patients who are diagnosed with coronavirus disease 2019 (COVID-19) suffer from venous thromboembolic complications despite the use of stringent anticoagulant prophylaxis. Studies on the exact mechanism(s) underlying thrombosis in COVID-19 are limited as animal models commonly used to study venous thrombosis pathophysiology (i.e. rats and mice) are naturally not susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Ferrets are susceptible to SARS-CoV-2 infection, successfully used to study virus transmission, and have been previously used to study activation of coagulation and thrombosis during influenza virus infection. Objectives: This study aimed to explore the use of (heat-inactivated) plasma and lung material from SARS-CoV-2-inoculated ferrets studying COVID-19-associated changes in coagulation and thrombosis. Material and methods: Histology and longitudinal plasma profiling using mass spectrometry-based proteomics approach was performed. Results: Lungs of ferrets inoculated intranasally with SARS-CoV-2 demonstrated alveolar septa that were mildly expanded by macrophages, and diffuse interstitial histiocytic pneumonia. However, no macroscopical or microscopical evidence of vascular thrombosis in the lungs of SARS-CoV-2-inoculated ferrets was found. Longitudinal plasma profiling revealed minor differences in plasma protein profiles in SARS-CoV-2-inoculated ferrets up to 2 weeks post-infection. The majority of plasma coagulation factors were stable and demonstrated a low coefficient of variation. Conclusions: We conclude that while ferrets are an essential and well-suited animal model to study SARS-CoV-2 transmission, their use to study SARS-CoV-2-related changes relevant to thrombotic disease is limited.

Published
2022

8. Identification of a novel deltavirus in Boa Constrictors

Author

Moscona, Anne, Moscona, A ( Anne ), Hetzel, Udo; https://orcid.org/0000-0001-9142-560X, Szirovicza, Leonóra; https://orcid.org/0000-0003-1528-044X, Smura, Teemu; https://orcid.org/0000-0002-9187-3151, Prähauser, Barbara, Vapalahti, Olli; https://orcid.org/0000-0003-2270-6824, Kipar, Anja; https://orcid.org/0000-0001-7289-3459, Hepojoki, Jussi; https://orcid.org/0000-0001-5699-214X, Moscona, Anne, Moscona, A ( Anne ), Hetzel, Udo; https://orcid.org/0000-0001-9142-560X, Szirovicza, Leonóra; https://orcid.org/0000-0003-1528-044X, Smura, Teemu; https://orcid.org/0000-0002-9187-3151, Prähauser, Barbara, Vapalahti, Olli; https://orcid.org/0000-0003-2270-6824, Kipar, Anja; https://orcid.org/0000-0001-7289-3459, and Hepojoki, Jussi; https://orcid.org/0000-0001-5699-214X

Abstract

Hepatitis D virus (HDV) forms the genus Deltavirus unassigned to any virus family. HDV is a satellite virus and needs hepatitis B virus (HBV) to make infectious particles. Deltaviruses are thought to have evolved in humans, since for a long time, they had not been identified elsewhere. Herein we report, prompted by the recent discovery of an HDV-like agent in birds, the identification of a deltavirus in snakes (Boa constrictor) designated snake HDV (sHDV). The circular 1,711-nt RNA genome of sHDV resembles human HDV (hHDV) in its coding strategy and size. We discovered sHDV during a metatranscriptomic study of brain samples of a Boa constrictor breeding pair with central nervous system signs. Applying next-generation sequencing (NGS) to brain, blood, and liver samples from both snakes, we did not find reads matching hepadnaviruses. Sequence comparison showed the snake delta antigen (sHDAg) to be 55% and 37% identical to its human and avian counterparts. Antiserum raised against recombinant sHDAg was used in immunohistology and demonstrated a broad viral target cell spectrum, including neurons, epithelial cells, and leukocytes. Using RT-PCR, we also detected sHDV RNA in two juvenile offspring and in a water python (Liasis mackloti savuensis) in the same snake colony, potentially indicating vertical and horizontal transmission. Screening of 20 randomly selected boas from another breeder by RT-PCR revealed sHDV infection in three additional snakes. The observed broad tissue tropism and the failure to detect accompanying hepadnavirus suggest that sHDV could be a satellite virus of a currently unknown enveloped virus. IMPORTANCE So far, the only known example of deltaviruses is the hepatitis delta virus (HDV). HDV is speculated to

Published
2019

9. M-Protein Peptides of Influenza Virus: Application as Antiviral Agents

Author

SRI INTERNATIONAL MENLO PARK CA LIFE SCIENCES DIV, Judd, Amrit K., Sanchez, Agustin, Kharitonenkov, Igor, Moscona, Anne, Nasser, Ezzeldin, SRI INTERNATIONAL MENLO PARK CA LIFE SCIENCES DIV, Judd, Amrit K., Sanchez, Agustin, Kharitonenkov, Igor, Moscona, Anne, and Nasser, Ezzeldin

Published
1992

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