Publications by authors named "Sara A Thannickal"
Article Synopsis
- Envelope proteins, specifically the E1 and E2 proteins of the Chikungunya virus (CHIKV), drive the fusion of the virus with host cell membranes, allowing the virus to enter cells.
- Research on CHIKV has shown that mutations in these proteins can confer resistance to antiviral treatments by enhancing fusion capabilities, particularly a double-mutant strain that tolerates a higher pH for effective fusion.
- Molecular dynamics simulations suggest that interactions between specific residues in these envelope proteins are crucial for their rearrangement during the fusion process, revealing important insights into viral infection mechanisms and potential therapeutic targets.
Article Synopsis
- Scientists studied a virus called chikungunya and found changes in its protein that affect how it infects cells.
- They discovered specific mutations in the virus’s E1 protein that change another protein called E2, making it easier for the virus to enter different types of cells.
- The study showed that these changes can make the virus infect more effectively in mosquitoes and certain cell types, which helps us understand how the virus spreads and could help fight it.
Unlabelled: The genomic determinants that contribute to orthobunyavirus infection and pathogenesis are not well-defined. In this study, we harnessed the process of reassortment to understand which viral factors drive change in the replication and pathogenesis of La Crosse virus (LACV). We systematically reassorted the genomic segments of two genetically similar Lineage I LACV isolates into six unique reassortants.
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- Alphaviruses, such as CHIKV, have different mechanisms for infecting mammals and insects, with this study focusing on specific variants of the E1 glycoprotein that affect host infection dynamics.
- The variants E1-N20Y and E1-M88L showed enhanced infectivity in mosquito and mammalian cells, respectively, suggesting that the E1 glycoprotein's structure plays a crucial role in virus binding and entry.
- The findings highlight the importance of understanding glycoprotein interactions and dynamics, as they influence the virus's ability to infect different cell types and hosts, which is vital given the public health implications of arboviruses.
Arthropod-borne viruses (arboviruses) are an emerging and evolving global public health threat, with limited antiviral treatments or vaccines available. La Crosse virus (LACV) from the order is responsible for pediatric encephalitis cases in the United States, yet little is known about the infectivity of LACV. Given the structural similarities between class II fusion glycoproteins of LACV and chikungunya virus (CHIKV), an alphavirus from the family, we hypothesized that LACV would share similar entry mechanisms with CHIKV.
View Article and Find Full Text PDFUnlabelled: Arthropod-borne viruses (arboviruses) are an emerging and evolving global public health threat with little to no antiviral treatments. La Crosse virus (LACV) from the order is responsible for pediatric encephalitis cases in the United States, yet little is known about the infectivity of LACV. Given the structural similarities between class II fusion glycoproteins of LACV and chikungunya virus (CHIKV), an alphavirus from the family, we hypothesized that LACV would share similar entry mechanisms to CHIKV.
View Article and Find Full Text PDFEpidemic RNA viruses seem to arise year after year leading to countless infections and devastating disease. SARS-CoV-2 is the most recent of these viruses, but there will undoubtedly be more to come. While effective SARS-CoV-2 vaccines are being deployed, one approach that is still missing is effective antivirals that can be used at the onset of infections and therefore prevent pandemics.
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- Alphaviruses and flaviviruses have similar class II fusion glycoproteins crucial for their assembly and infectivity, specifically noting conservation in the tip of domain II among both virus families.
- Research on Zika virus identified a novel envelope glycoprotein variant that, while minimally affecting infection in mosquitoes, reduced viral replication in human cells and mice and heightened sensitivity to ammonium chloride.
- The study further explored mutations in the flavivirus E β-strand c and ij loop, revealing that certain alterations can inhibit the production of infectious Zika and yellow fever viruses, suggesting that structural similarities in these glycoproteins play significant roles in viral infection and could inform antiviral strategies.
Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation.
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- The COVID-19 pandemic, caused by SARS-CoV-2, has prompted a global effort to create effective vaccines, with a need for alternatives that provide long-term protection and are cost-effective to manufacture.
- Researchers have developed a new vaccine using a Sindbis alphavirus vector expressing the SARS-CoV-2 spike protein combined with an OX40 immunostimulatory antibody, which has shown promising results in eliciting strong immune responses in mice.
- This novel vaccine approach not only produced lasting neutralizing antibodies and a vigorous T-cell response but also provided effective protection against the coronavirus in mice, highlighting its potential as a candidate for tackling SARS-CoV-2 and other pathogens.
Article Synopsis
- Antibody responses are crucial for defending against SARS-CoV-2 by stopping the virus from entering cells, and a new assay called 2D-MBBA has been developed to measure various antibody isotypes simultaneously.
- This assay was used to analyze IgG, IgM, and IgA levels against the spike protein and its variants, and machine learning significantly improved predictions of how well these antibodies neutralize the virus in convalescent patients.
- The method can differentiate between antibody profiles in convalescent and vaccinated individuals and offers the potential for rapid testing of neutralization efficacy against new variants and pathogens using just a small blood sample.
Article Synopsis
- Patients with hematologic malignancies, such as non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), show a significantly reduced humoral response to SARS-CoV-2 vaccinations, indicating a potential gap in vaccine efficacy for these individuals.
- A study of 53 patients revealed that most had low antibody levels and only a small percentage generated neutralizing antibodies after vaccination, especially among those receiving certain therapies like anti-CD20 treatment.
- Given these findings, it's recommended that patients with these conditions maintain safety precautions like masking and social distancing, as their immunity may not be sufficient even post-vaccination.
Article Synopsis
- The COVID-19 pandemic, caused by SARS-CoV-2, has led to a global push for effective vaccine development, highlighting the need for new alternatives that ensure long-term protection and can be produced affordably at scale.
- Researchers have developed a novel vaccine using a Sindbis alphavirus vector that expresses the SARS-CoV-2 spike protein combined with an immunostimulatory antibody, showing strong immune responses in mice, including the production of neutralizing antibodies and T-cell activation.
- The study suggests this vaccine platform not only offers significant protection against SARS-CoV-2 but also shows promise for broader applications against other pathogens and variants.
Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation.
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