26 results on '"Priyamvada, Lalita"'
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2. Prevalence of Undiagnosed Monkeypox Virus Infections during Global Mpox Outbreak, United States, June-September 2022
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Minhaj, Faisal S., Singh, Vjay, Cohen, Stephanie E., Townsend, Michael, Scott, Hyman, Szumowski, John, Hare, C. Bradley, Upadhyay, Pallavi, Reddy, Jairus, Alexander, Barbara, Baird, Nicolle, Navarra, Terese, Priyamvada, Lalita, Wynn, Nhien, Carson, William C., Odafe, Solomon, Guagliardo, Sarah Anne J., Sims, Emily, Rao, Agam K., Satheshkumar, Panayampalli S., Weidle, Paul J., and Hutson, Christina L.
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Human monkeypox -- Diagnosis -- Care and treatment ,MSM (Men who have sex with men) -- Health aspects ,Medical statistics -- Evaluation ,Health - Abstract
Since May 2022, monkeypox virus (MPXV) infections have been detected in 108 countries without endemic disease. Most cases have been among gay, bisexual, or other men who have sex with [...]
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- 2023
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3. Serologic responses to the MVA-based JYNNEOS mpox vaccine in a cohort of participants from the District of Columbia (D.C.)
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Griffin, Isabel, Berry, Isha, Navarra, Terese, Priyamvada, Lalita, Carson, William C., Noiman, Adi, Jackson, David A., Waltenburg, Michelle A., Still, Will, Lujan, Leah, Beverley, Jason, Willut, Christina, Lee, Michelle, Mangla, Anil, Shelus, Victoria, Hutson, Christina L., Townsend, Michael B., and Satheshkumar, Panayampalli S.
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- 2024
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4. Antiviral activities of two nucleos(t)ide analogs against vaccinia, mpox, and cowpox viruses in primary human fibroblasts
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Dsouza, Lara, Pant, Anil, Offei, Samuel, Priyamvada, Lalita, Pope, Blake, Satheshkumar, Panayampalli S., Wang, Zhengqiang, and Yang, Zhilong
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- 2023
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5. Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo
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Priyamvada, Lalita, Carson, William C., Ortega, Eddy, Navarra, Terese, Tran, Stephanie, Smith, Todd G., Pukuta, Elisabeth, Muyamuna, Elisabeth, Kabamba, Joelle, Nguete, Beatrice U., Likafi, Toutou, Kokola, Gaston, Lushima, Robert Shongo, Tamfum, Jean-Jacques Muyembe, Okitolonda, Emile W., Kaba, Didine K., Monroe, Benjamin P., McCollum, Andrea M., Petersen, Brett W., Satheshkumar, Panayampalli S., and Townsend, Michael B.
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- 2022
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6. Serological Evidence of Mpox Virus Infection During Peak Mpox Transmission in New York City, July to August 2022.
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Pathela, Preeti, Townsend, Michael B, Kopping, Erik J, Tang, Jennifer, Navarra, Terese, Priyamvada, Lalita, Carson, William C, Panayampalli, S Satheshkumar, Fowler, Randal C, Kyaw, Nang, Hughes, Scott, and Jamison, Kelly
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Background The extent to which infections may have been undetected in an epicenter of the 2022 mpox outbreak is unknown. Methods A serosurvey (July and August 2022) assessed the seroprevalence and correlates of mpox infection among a diverse sample of asymptomatic patients with no prior mpox diagnoses and no known histories of smallpox or mpox vaccination. We present seropositivity stratified by participant characteristics collected via survey. Results Two-thirds of 419 participants were cismen (281 of 419), of whom 59.1% (166 of 281) reported sex with men (MSM). The sample also included 109 ciswomen and 28 transgender/gender nonconforming/nonbinary individuals. Overall seroprevalence was 6.4% (95% confidence interval [CI], 4.1%–8.8%); 3.7% among ciswomen (95% CI, 1.0%–9.1%), 7.0% among cismen with only ciswomen partners (95% CI, 2.0%–11.9%), and 7.8% among MSM (95% CI, 3.7%–11.9%). There was little variation in seroprevalence by race/ethnicity, age group, HIV status, or number of recent sex partners. No participants who reported close contact with mpox cases were seropositive. Among participants without recent mpox-like symptoms, 6.3% were seropositive (95% CI, 3.6%–9.0%). Conclusions Approximately 1 in 15 vaccine-naive people in our study had antibodies to mpox during the height of the NYC outbreak, indicating the presence of asymptomatic infections that could contribute to ongoing transmission. [ABSTRACT FROM AUTHOR]
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- 2024
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7. SARS-CoV-2–Associated Deaths Among Persons Aged
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Pediatric Mortality Investigation Team, Bixler, Danae, Miller, Allison D., Mattison, Claire P., Taylor, Burnestine, Komatsu, Kenneth, Pompa, Xandy Peterson, Moon, Steve, Karmarkar, Ellora, Liu, Caterina Y., Openshaw, John J., Plotzker, Rosalyn E., Rosen, Hilary E., Alden, Nisha, Kawasaki, Breanna, Siniscalchi, Alan, Leapley, Andrea, Drenzek, Cherie, Tobin-D’Angelo, Melissa, Kauerauf, Judy, Reid, Heather, Hawkins, Eric, White, Kelly, Ahmed, Farah, Hand, Julie, Richardson, Gillian, Sokol, Theresa, Eckel, Seth, Collins, Jim, Holzbauer, Stacy, Kollmann, Leslie, Larson, Linnea, Schiffman, Elizabeth, Kittle, Theresa S., Hertin, Kimberly, Kraushaar, Vit, Raman, Devin, LeGarde, Victoria, Kinsinger, Lindsey, Peek-Bullock, Melissa, Lifshitz, Jenna, Ojo, Mojisola, Arciuolo, Robert J, Davidson, Alexander, Huynh, Mary, Lash, Maura K., Latash, Julia, Lee, Ellen H., Li, Lan, McGibbon, Emily, McIntosh-Beckles, Natasha, Pouchet, Renee, Ramachandran, Jyotsna S., Reilly, Kathleen H., Dufort, Elizabeth, Pulver, Wendy, Zamcheck, Ariela, Wilson, Erica, de Fijter, Sietske, Naqvi, Ozair, Nalluswami, Kumar, Waller, Kirsten, Bell, Linda J., Burch, Anna-Kathryn, Radcliffe, Rachel, Fiscus, Michelle D., Lewis, Adele, Kolsin, Jonathan, Pont, Stephen, Salinas, Andrea, Sanders, Kelsey, Barbeau, Bree, Althomsons, Sandy, Atti, Sukhshant, Brown, Jessica S., Chang, Arthur, Clarke, Kevin R., Datta, S. Deblina, Iskander, John, Leitgeb, Brooke, Pindyck, Talia, Priyamvada, Lalita, Reagan-Steiner, Sarah, Scott, Nigel A., Viens, Laura J., Zhong, Jonathan, and Koumans, Emilia H.
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- 2020
8. Analysis of dengue specific memory B cells, neutralizing antibodies and binding antibodies in healthy adults from India
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Gunisetty, Sivaram, Nayak, Kaustuv, Chandra Rai, Ramesh, Chawla, Yadya, Reddy, Elluri Seetharami, Aggarwal, Charu, Maheshwari, Deepti, Panda, Harekrushna, Ansari, Nasim Akhtar, Singh, Prabhat, Kaur, Manpreet, Dixit, Kritika, Sharma, Pragati, Bhatnagar, Priya, Priyamvada, Lalita, Bhaumik, Siddhartha Kumar, Ahamed, Syed Fazil, Vivek, Rosario, Ray, Pratima, Shet, Anita, Coshic, Poonam, Lodha, Rakesh, Kabra, Sushil Kumar, Afroze, Dil, Yousuf, Adfar, Ahmed, Rafi, Murali-Krishna, Kaja, and Chandele, Anmol
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- 2019
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9. Humoral Immune Responses Against Zika Virus Infection and the Importance of Preexisting Flavivirus Immunity
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Priyamvada, Lalita, Suthar, Mehul S., Ahmed, Rafi, and Wrammert, Jens
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- 2017
10. Human antibody responses after dengue virus infection are highly cross-reactive to Zika virus
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Priyamvada, Lalita, Quicke, Kendra M., Hudson, William H., Onlamoon, Nattawat, Sewatanon, Jaturong, Edupuganti, Srilatha, Pattanapanyasat, Kovit, Chokephaibulkit, Kulkanya, Mulligan, Mark J., Wilson, Patrick C., Ahmed, Rafi, Suthar, Mehul S., and Wrammert, Jens
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- 2016
11. Evidence of Mpox Virus Infection Among Persons Without Characteristic Lesions or Rash Presenting for First Dose of JYNNEOS Vaccine—District of Columbia, August 2022.
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Ogale, Yasmin P, Baird, Nicolle, Townsend, Michael B, Berry, Isha, Griffin, Isabel, Lee, Michelle, Ashley, Patrick, Rhodes, Trevor, Notigan, Tiffany, Wynn, Nhien, Kling, Chantal, Smith, Todd, Priyamvada, Lalita, Carson, William C, Navarra, Terese, Dawson, Patrick, Weidle, Paul J, Willut, Christina, Mangla, Anil T, and Satheshkumar, Panayampalli S
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PREVENTION of infectious disease transmission ,IMMUNIZATION ,MONKEYPOX ,EXANTHEMA ,SMALLPOX vaccines ,RISK assessment ,DISEASE risk factors ,INFECTIOUS disease transmission ,SYMPTOMS - Abstract
We assessed mpox virus prevalence in blood, pharyngeal, and rectal specimens among persons without characteristic rash presenting for JYNNEOS vaccine. Our data indicate that the utility of risk-based screening for mpox in persons without skin lesions or rash via pharyngeal swabs, rectal swabs, and/or blood is likely limited. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Inhibition of vaccinia virus L1 N-myristoylation by the host N-myristoyltransferase inhibitor IMP-1088 generates non-infectious virions defective in cell entry.
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Priyamvada, Lalita, Kallemeijn, Wouter W., Faronato, Monica, Wilkins, Kimberly, Goldsmith, Cynthia S., Cotter, Catherine A., Ojeda, Suany, Solari, Roberto, Moss, Bernard, Tate, Edward W., and Satheshkumar, Panayampalli Subbian
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VACCINIA , *POST-translational modification , *VIRAL proteins , *LIFE cycles (Biology) , *SMALL molecules , *MEMBRANE fusion , *CELL fusion - Abstract
We have recently shown that the replication of rhinovirus, poliovirus and foot-and-mouth disease virus requires the co-translational N-myristoylation of viral proteins by human host cell N-myristoyltransferases (NMTs), and is inhibited by treatment with IMP-1088, an ultrapotent small molecule NMT inhibitor. Here, we examine the importance of N-myristoylation during vaccinia virus (VACV) infection in primate cells and demonstrate the anti-poxviral effects of IMP-1088. N-myristoylated proteins from VACV and the host were metabolically labelled with myristic acid alkyne during infection using quantitative chemical proteomics. We identified VACV proteins A16, G9 and L1 to be N-myristoylated. Treatment with NMT inhibitor IMP-1088 potently abrogated VACV infection, while VACV gene expression, DNA replication, morphogenesis and EV formation remained unaffected. Importantly, we observed that loss of N-myristoylation resulted in greatly reduced infectivity of assembled mature virus particles, characterized by significantly reduced host cell entry and a decline in membrane fusion activity of progeny virus. While the N-myristoylation of VACV entry proteins L1, A16 and G9 was inhibited by IMP-1088, mutational and genetic studies demonstrated that the N-myristoylation of L1 was the most critical for VACV entry. Given the significant genetic identity between VACV, monkeypox virus and variola virus L1 homologs, our data provides a basis for further investigating the role of N-myristoylation in poxviral infections as well as the potential of selective NMT inhibitors like IMP-1088 as broad-spectrum poxvirus inhibitors. Author summary: N-myristoylation is a lipidic co- or post-translational modification of proteins that is catalyzed by the enzyme N-myristoyltransferase (NMT). In this study, we use IMP-1088, an ultrapotent inhibitor of human NMTs, to query whether targeting the N-myristolation of viral proteins can serve as an effective antiviral strategy against VACV. Through quantitative chemical proteomics, we demonstrated that IMP-1088 blocks the N-myristoylation of L1, a VACV protein essential for viral entry. Progeny virus particles generated in the presence of IMP-1088 lacked N-myrisoylated L1, which considerably reduced their infectivity. Other steps in the viral life cycle, including replication, morphogenesis and viral egress were not directly impacted by IMP-1088-mediated NMT inhibition. While the N-myristoylation of two other EFC proteins, namely A16 and G9, was also abrogated by IMP-1088 treatment, mutational studies revealed they were dispensable for viral entry in the presence of a functional L1 protein. Taken together, these data illustrate the mechanism of action of IMP-1088 as a potential poxviral inhibitor. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Discovery of Retro-1 Analogs Exhibiting Enhanced Anti-vaccinia Virus Activity.
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Priyamvada, Lalita, Alabi, Philip, Leon, Andres, Kumar, Amrita, Sambhara, Suryaprakash, Olson, Victoria A., Sello, Jason K., and Satheshkumar, Panayampalli S.
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VACCINIA ,VIRUSES ,ANTIVIRAL agents ,SMALLPOX ,SMALL molecules ,ORTHOPOXVIRUSES - Abstract
Orthopoxviruses (OPXVs) are an increasing threat to human health due to the growing population of OPXV-naive individuals after the discontinuation of routine smallpox vaccination. Antiviral drugs that are effective as postexposure treatments against variola virus (the causative agent of smallpox) or other OPXVs are critical in the event of an OPXV outbreak or exposure. The only US Food and Drug Administration-approved drug to treat smallpox, Tecovirimat (ST-246), exerts its antiviral effect by inhibiting extracellular virus (EV) formation, thereby preventing cell–cell and long-distance spread. We and others have previously demonstrated that host Golgi-associated retrograde proteins play an important role in monkeypox virus (MPXV) and vaccinia virus (VACV) EV formation. Inhibition of the retrograde pathway by small molecules such as Retro-2 has been shown to decrease VACV infection in vitro and to a lesser extent in vivo. To identify more potent inhibitors of the retrograde pathway, we screened a large panel of compounds containing a benzodiazepine scaffold like that of Retro-1, against VACV infection. We found that a subset of these compounds displayed better anti-VACV activity, causing a reduction in EV particle formation and viral spread compared to Retro-1. PA104 emerged as the most potent analog, inhibiting 90% viral spread at 1.3 μM with a high selectivity index. In addition, PA104 strongly inhibited two distinct ST-246-resistant viruses, demonstrating its potential benefit for use in combination therapy with ST-246. These data and further characterizations of the specific protein targets and in vivo efficacy of PA104 may have important implications for the design of effective antivirals against OPXV. [ABSTRACT FROM AUTHOR]
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- 2020
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14. Humoral cross-reactivity between Zika and dengue viruses: implications for protection and pathology.
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Priyamvada, Lalita, Hudson, William, Ahmed, Rafi, and Wrammert, Jens
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- 2017
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15. B Cell Responses during Secondary Dengue Virus Infection Are Dominated by Highly Cross-Reactive, Memory-Derived Plasmablasts.
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Priyamvada, Lalita, Cho, Alice, Onlamoon, Nattawat, Nai-Ying Zheng, Min Huang, Kovalenkov, Yevgeniy, Chokephaibulkit, Kulkanya, Angkasekwinai, Nasikarn, Pattanapanyasat, Kovit, Ahmed, Rafi, Wilson, Patrick C., and Wrammert, Jens
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DENGUE viruses , *B cells , *EPIDEMIOLOGY , *GENETIC mutation , *PATHOGENIC viruses - Abstract
Dengue virus (DENV) infection results in the production of both type-specific and cross-neutralizing antibodies. While immunity to the infecting serotype is long-lived, heterotypic immunity wanes a few months after infection. Epidemiological studies link secondary heterotypic infections with more severe symptoms, and cross-reactive, poorly neutralizing antibodies have been implicated in this increased disease severity. To understand the cellular and functional properties of the acute dengue virus B cell response and its role in protection and immunopathology, we characterized the plasmablast response in four secondary DENV type 2 (DENV2) patients. Dengue plasmablasts had high degrees of somatic hypermutation, with a clear preference for replacement mutations. Clonal expansions were also present in each donor, strongly supporting a memory origin for these acutely induced cells. We generated 53 monoclonal antibodies (MAbs) from sorted patient plasmablasts and found that DENV-reactive MAbs were largely envelope specific and cross neutralizing. Many more MAbs neutralized DENV than reacted to envelope protein, emphasizing the significance of virion-dependent B cell epitopes and the limitations of envelope protein-based antibody screening. A majority of DENV-reactive MAbs, irrespective of neutralization potency, enhanced infection by antibody-dependent enhancement (ADE). Interestingly, even though DENV2 was the infecting serotype in all four patients, several MAbs from two patients neutralized DENV1 more potently than DENV2. Further, half of all type-specific neutralizing MAbs were also DENV1 biased in binding. Taken together, these findings are reminiscent of original antigenic sin (OAS), given that the patients had prior dengue virus exposures. These data describe the ongoing B cell response in secondary patients and may further our understanding of the impact of antibodies in dengue virus pathogenesis. [ABSTRACT FROM AUTHOR]
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- 2016
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16. Gammaherpesvirus Co-infection with Malaria Suppresses Anti-parasitic Humoral Immunity.
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Matar, Caline G., Anthony, Neil R., O’Flaherty, Brigid M., Jacobs, Nathan T., Priyamvada, Lalita, Engwerda, Christian R., Speck, Samuel H., and Lamb, Tracey J.
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HERPESVIRUSES ,MIXED infections ,PLASMODIUM falciparum ,MALARIA ,B cells - Abstract
Immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for Plasmodium falciparum. Yet, nearly 20% of infected children die annually as a result of severe malaria. Multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. Children living in Sub-Saharan Africa are seropositive for Epstein Barr Virus (EBV) by the age of 6 months. This timing overlaps with the waning of protective maternal antibodies and susceptibility to primary Plasmodium infection. However, the impact of acute EBV infection on the generation of anti-malarial immunity is unknown. Using well established mouse models of infection, we show here that acute, but not latent murine gammaherpesvirus 68 (MHV68) infection suppresses the anti-malarial humoral response to a secondary malaria infection. Importantly, this resulted in the transformation of a non-lethal P. yoelii XNL infection into a lethal one; an outcome that is correlated with a defect in the maintenance of germinal center B cells and T follicular helper (Tfh) cells in the spleen. Furthermore, we have identified the MHV68 M2 protein as an important virus encoded protein that can: (i) suppress anti-MHV68 humoral responses during acute MHV68 infection; and (ii) plays a critical role in the observed suppression of anti-malarial humoral responses in the setting of co-infection. Notably, co-infection with an M2-null mutant MHV68 eliminates lethality of P. yoelii XNL. Collectively, our data demonstrates that an acute gammaherpesvirus infection can negatively impact the development of an anti-malarial immune response. This suggests that acute infection with EBV should be investigated as a risk factor for non-cerebral severe malaria in young children living in areas endemic for Plasmodium transmission. [ABSTRACT FROM AUTHOR]
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- 2015
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17. Influenza Virus Reassortment Occurs with High Frequency in the Absence of Segment Mismatch.
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Marshall, Nicolle, Priyamvada, Lalita, Ende, Zachary, Steel, John, and Lowen, Anice C.
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INFLUENZA viruses , *INFLUENZAVIRUS A , *GUINEA pigs as laboratory animals , *ORTHOMYXOVIRUSES , *RNA viruses - Abstract
Reassortment is fundamental to the evolution of influenza viruses and plays a key role in the generation of epidemiologically significant strains. Previous studies indicate that reassortment is restricted by segment mismatch, arising from functional incompatibilities among components of two viruses. Additional factors that dictate the efficiency of reassortment remain poorly characterized. Thus, it is unclear what conditions are favorable for reassortment and therefore under what circumstances novel influenza A viruses might arise in nature. Herein, we describe a system for studying reassortment in the absence of segment mismatch and exploit this system to determine the baseline efficiency of reassortment and the effects of infection dose and timing. Silent mutations were introduced into A/Panama/2007/99 virus such that high-resolution melt analysis could be used to differentiate all eight segments of the wild-type and the silently mutated variant virus. The use of phenotypically identical parent viruses ensured that all progeny were equally fit, allowing reassortment to be measured without selection bias. Using this system, we found that reassortment occurred efficiently (88.4%) following high multiplicity infection, suggesting the process is not appreciably limited by intracellular compartmentalization. That co-infection is the major determinant of reassortment efficiency in the absence of segment mismatch was confirmed with the observation that the proportion of viruses with reassortant genotypes increased exponentially with the proportion of cells co-infected. The number of reassortants shed from co-infected guinea pigs was likewise dependent on dose. With 106 PFU inocula, 46%–86% of viruses isolated from guinea pigs were reassortants. The introduction of a delay between infections also had a strong impact on reassortment and allowed definition of time windows during which super-infection led to reassortment in culture and in vivo. Overall, our results indicate that reassortment between two like influenza viruses is efficient but also strongly dependent on dose and timing of the infections. [ABSTRACT FROM AUTHOR]
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- 2013
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18. New methylene blue derivatives suggest novel anti-orthopoxviral strategies.
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Priyamvada, Lalita, Burgado, Jillybeth, Baker-Wagner, Marissa, Kitaygorodskyy, Anatoliy, Olson, Victoria, Lingappa, Vishwanath R., and Satheshkumar, Panayampalli Subbian
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VACCINIA , *METHYLENE blue , *SMALLPOX vaccines , *SMALL molecules , *SMALLPOX , *VACCINATION - Abstract
Decades after the eradication of smallpox and the discontinuation of routine smallpox vaccination, over half of the world's population is immunologically naïve to variola virus and other orthopoxviruses (OPXVs). Even in those previously vaccinated against smallpox, protective immunity wanes over time. As such, there is a concomitant increase in the incidence of human OPXV infections worldwide. To identify novel antiviral compounds with potent anti-OPXV potential, we characterized the inhibitory activity of PAV-866 and other methylene blue derivatives against the prototypic poxvirus, vaccinia virus (VACV). These compounds inactivated virions prior to infection and consequently inhibited viral binding, fusion and entry. The compounds exhibited strong virucidal activity at non-cytotoxic concentrations, and inhibited VACV infection when added before, during or after viral adsorption. The compounds were effective against other OPXVs including monkeypox virus, cowpox virus and the newly identified Akhmeta virus. Altogether, these findings reveal a novel mode of inhibition that has not previously been demonstrated for small molecule compounds against VACV. Additional studies are in progress to determine the in vivo efficacy of these compounds against OPXVs and further characterize the anti-viral effects of these derivatives. • Demonstrated anti-poxvirus activity of novel methylene blue derivatives. • Compounds exhibited direct inhibitory effect on viral particles. • Compounds exhibit antiviral effects against other orthopoxviruses including monkeypox, cowpox and Akhmeta virus. [ABSTRACT FROM AUTHOR]
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- 2021
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19. Conserved Oligomeric Golgi (COG) Complex Proteins Facilitate Orthopoxvirus Entry, Fusion and Spread.
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Realegeno, Susan, Priyamvada, Lalita, Kumar, Amrita, Blackburn, Jessica B., Hartloge, Claire, Puschnik, Andreas S., Sambhara, Suryaprakash, Olson, Victoria A., Carette, Jan E., Lupashin, Vladimir, and Satheshkumar, Panayampalli Subbian
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GENETIC testing , *VACCINIA , *MEMBRANE proteins , *PLASMIDS , *GENE knockout , *HAPLOIDY - Abstract
Although orthopoxviruses (OPXV) are known to encode a majority of the genes required for replication in host cells, genome-wide genetic screens have revealed that several host pathways are indispensable for OPXV infection. Through a haploid genetic screen, we previously identified several host genes required for monkeypox virus (MPXV) infection, including the individual genes that form the conserved oligomeric Golgi (COG) complex. The COG complex is an eight-protein (COG1–COG8) vesicle tethering complex important for regulating membrane trafficking, glycosylation enzymes, and maintaining Golgi structure. In this study, we investigated the role of the COG complex in OPXV infection using cell lines with individual COG gene knockout (KO) mutations. COG KO cells infected with MPXV and vaccinia virus (VACV) produced small plaques and a lower virus yield compared to wild type (WT) cells. In cells where the KO phenotype was reversed using a rescue plasmid, the size of virus plaques increased demonstrating a direct link between the decrease in viral spread and the KO of COG genes. KO cells infected with VACV displayed lower levels of viral fusion and entry compared to WT suggesting that the COG complex is important for early events in OPXV infection. Additionally, fewer actin tails were observed in VACV-infected KO cells compared to WT. Since COG complex proteins are required for cellular trafficking of glycosylated membrane proteins, the disruption of this process due to lack of individual COG complex proteins may potentially impair the virus-cell interactions required for viral entry and egress. These data validate that the COG complex previously identified in our genetic screens plays a role in OPXV infection. [ABSTRACT FROM AUTHOR]
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- 2020
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20. Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine.
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Anderson, Evan J., Lai, Lilin, Wrammert, Jens, Kabbani, Sarah, Xu, Yongxian, Priyamvada, Lalita, Hill, Heather, Goll, Johannes B., Jensen, Travis L., Kao, Carol, Yildirim, Inci, Rouphael, Nadine, Jackson, Lisa, and Mulligan, Mark J.
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T helper cells ,B cells ,T cells ,VACCINIA ,VACCINES - Abstract
Background: Vaccinia is known to induce antibody and cellular responses. Plasmablast, circulating follicular helper T (cT
FH ) cells, cytokine-expressing CD4 T cells, and memory B cells were compared between subcutaneous (SC) and needle-free jet injection (JI) recipients of non-replicating modified vaccinia Ankara (MVA) vaccine. Methods: Vaccinia-naïve adults received MVA SC or by JI on Days 1 and 29. Vaccinia-specific antibodies were quantified by plaque reduction neutralization test (PRNT) and enzyme-linked immunosorbent assay. Plasmablast, cTFH , and cytokine-expressing CD4 T cells were assessed on Days 1, 8, 15, 29, 36, 43 (cTFH and CD4+ only) and 57. Memory B cells were measured on Days 1 and 57. Results: Of the 36 enrolled subjects, only 22 received both vaccinations and had evaluable specimens after the second vaccine. Plasmablasts peaked one week after each vaccine. Day 15 plasmablasts correlated with peak PRNT titers. cTFH peaked on Days 8 and 36 and correlated with Day 36 plasmablasts. CD4+ peaked at Day 29 and one-third produced ≥2 cytokines. Day 57 memory B cells ranged from 0.1% to 0.17% of IgG-secreting B cells. Conclusions: This study provides insights into the cellular responses to non-replicating MVA, currently used as a vector for a variety of novel vaccines. [ABSTRACT FROM AUTHOR]- Published
- 2020
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21. Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient.
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Bhaumik, Siddhartha K., Priyamvada, Lalita, Kauffman, Robert C., Lai, Lilin, Natrajan, Muktha S., Cho, Alice, Rouphael, Nadine, Suthar, Mehul S., Mulligan, Mark J., and Wrammert, Jens
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ZIKA virus infections , *DENGUE viruses , *B cells , *IMMUNE response , *GENE expression - Abstract
The re-emergence of Zika virus (ZIKV) in the western hemisphere has most significantly affected dengue virus (DENV) endemic regions. Due to the geographical overlap between these two closely related flaviviruses, numerous individuals who suffered ZIKV infection during recent outbreaks may have also previously been exposed to DENV. As such, the impact of pre-existing dengue immunity on immune responses to ZIKV has been an area of focused research and interest. To understand how B cell responses to a ZIKV infection may be modulated by prior dengue exposures, we compared and contrasted plasmablast repertoire and specificity between two ZIKV-infected individuals, one dengue-naïve (ZK018) and the other dengue-experienced (ZK016). In addition to examining serological responses, we generated 59 patient plasmablast-derived monoclonal antibodies (mAbs) to define the heterogeneity of the early B cell response to ZIKV. Both donors experienced robust ZIKV-induced plasmablast expansions early after infection, with comparable mutational frequencies in their antibody variable genes. However, notable differences were observed in plasmablast clonality and functional reactivity. Plasmablasts from the dengue-experienced donor ZK016 included cells with shared clonal origin, while ZK018 mAbs were entirely clonally unrelated. Both at the mAb and plasma level, ZK016 antibodies displayed extensive cross-reactivity to DENV1-4, and preferentially neutralized DENV compared to ZIKV. In contrast, the neutralization activity of ZK018 mAbs was primarily directed towards ZIKV, and fewer mAbs from this donor were cross-reactive, with the cross-reactive phenotype largely limited to fusion loop-specific mAbs. ZK016 antibodies caused greater enhancement of DENV2 infection of FcRγ-expressing cells overall compared to ZK018, with a striking difference at the plasma level. Taken together, these data strongly suggest that the breadth and protective capacity of the initial antibody responses after ZIKV infection may depend on the dengue immune status of the individual. These findings have implications for vaccine design, given the likelihood that future epidemics will involve both dengue-experienced and naïve populations. [ABSTRACT FROM AUTHOR]
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- 2019
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22. Antiviral activities of two nucleos(t)ide analogs against vaccinia and mpox viruses in primary human fibroblasts.
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Dsouza L, Pant A, Offei S, Priyamvada L, Pope B, Satheshkumar PS, Wang Z, and Yang Z
- Abstract
Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox. Identification of inhibitors of poxvirus replication is critical for drug development to manage poxvirus threats. Here we tested two compounds, nucleoside trifluridine and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV) and mpox virus (MPXV) in physiologically relevant primary human fibroblasts. Both trifluridine and adefovir dipivoxil potently inhibited replication of VACV and MPXV (MA001 2022 isolate) in a plaque assay. Upon further characterization, they both conferred high potency in inhibiting VACV replication with half maximal effective concentrations (EC
50 ) at low nanomolar levels in our recently developed assay based on a recombinant VACV secreted Gaussia luciferase. Our results further validated that the recombinant VACV with Gaussia luciferase secretion is a highly reliable, rapid, non-disruptive, and simple reporter tool for identification and chracterization of poxvirus inhibitors. Both compounds inhibited VACV DNA replication and downstream viral gene expression. Given that both compounds are FDA-approved drugs, and trifluridine is used to treat ocular vaccinia in medical practice due to its antiviral activity, our results suggest that it holds great promise to further test trifluridine and adefovir dipivoxil for countering poxvirus infection, including mpox.- Published
- 2023
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23. SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years - United States, February 12-July 31, 2020.
- Author
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Bixler D, Miller AD, Mattison CP, Taylor B, Komatsu K, Peterson Pompa X, Moon S, Karmarkar E, Liu CY, Openshaw JJ, Plotzker RE, Rosen HE, Alden N, Kawasaki B, Siniscalchi A, Leapley A, Drenzek C, Tobin-D'Angelo M, Kauerauf J, Reid H, Hawkins E, White K, Ahmed F, Hand J, Richardson G, Sokol T, Eckel S, Collins J, Holzbauer S, Kollmann L, Larson L, Schiffman E, Kittle TS, Hertin K, Kraushaar V, Raman D, LeGarde V, Kinsinger L, Peek-Bullock M, Lifshitz J, Ojo M, Arciuolo RJ, Davidson A, Huynh M, Lash MK, Latash J, Lee EH, Li L, McGibbon E, McIntosh-Beckles N, Pouchet R, Ramachandran JS, Reilly KH, Dufort E, Pulver W, Zamcheck A, Wilson E, de Fijter S, Naqvi O, Nalluswami K, Waller K, Bell LJ, Burch AK, Radcliffe R, Fiscus MD, Lewis A, Kolsin J, Pont S, Salinas A, Sanders K, Barbeau B, Althomsons S, Atti S, Brown JS, Chang A, Clarke KR, Datta SD, Iskander J, Leitgeb B, Pindyck T, Priyamvada L, Reagan-Steiner S, Scott NA, Viens LJ, Zhong J, and Koumans EH
- Subjects
- Adolescent, COVID-19, Cause of Death trends, Child, Child, Preschool, Female, Humans, Infant, Male, Pandemics, United States epidemiology, Young Adult, Coronavirus Infections complications, Coronavirus Infections mortality, Pneumonia, Viral complications, Pneumonia, Viral mortality
- Abstract
Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).
† These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.- Published
- 2020
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24. Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient.
- Author
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Bhaumik SK, Priyamvada L, Kauffman RC, Lai L, Natrajan MS, Cho A, Rouphael N, Suthar MS, Mulligan MJ, and Wrammert J
- Subjects
- Adult, Antibodies, Monoclonal immunology, Antibodies, Neutralizing blood, Antibodies, Viral blood, Dengue Virus, Female, Humans, B-Lymphocytes immunology, Cross Reactions, Dengue immunology, Immunologic Memory, Plasma Cells immunology, Zika Virus Infection immunology
- Abstract
The re-emergence of Zika virus (ZIKV) in the western hemisphere has most significantly affected dengue virus (DENV) endemic regions. Due to the geographical overlap between these two closely related flaviviruses, numerous individuals who suffered ZIKV infection during recent outbreaks may have also previously been exposed to DENV. As such, the impact of pre-existing dengue immunity on immune responses to ZIKV has been an area of focused research and interest. To understand how B cell responses to a ZIKV infection may be modulated by prior dengue exposures, we compared and contrasted plasmablast repertoire and specificity between two ZIKV-infected individuals, one dengue-naïve (ZK018) and the other dengue-experienced (ZK016). In addition to examining serological responses, we generated 59 patient plasmablast-derived monoclonal antibodies (mAbs) to define the heterogeneity of the early B cell response to ZIKV. Both donors experienced robust ZIKV-induced plasmablast expansions early after infection, with comparable mutational frequencies in their antibody variable genes. However, notable differences were observed in plasmablast clonality and functional reactivity. Plasmablasts from the dengue-experienced donor ZK016 included cells with shared clonal origin, while ZK018 mAbs were entirely clonally unrelated. Both at the mAb and plasma level, ZK016 antibodies displayed extensive cross-reactivity to DENV1-4, and preferentially neutralized DENV compared to ZIKV. In contrast, the neutralization activity of ZK018 mAbs was primarily directed towards ZIKV, and fewer mAbs from this donor were cross-reactive, with the cross-reactive phenotype largely limited to fusion loop-specific mAbs. ZK016 antibodies caused greater enhancement of DENV2 infection of FcRγ-expressing cells overall compared to ZK018, with a striking difference at the plasma level. Taken together, these data strongly suggest that the breadth and protective capacity of the initial antibody responses after ZIKV infection may depend on the dengue immune status of the individual. These findings have implications for vaccine design, given the likelihood that future epidemics will involve both dengue-experienced and naïve populations.
- Published
- 2018
- Full Text
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25. Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages.
- Author
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Zimmerman MG, Quicke KM, O'Neal JT, Arora N, Machiah D, Priyamvada L, Kauffman RC, Register E, Adekunle O, Swieboda D, Johnson EL, Cordes S, Haddad L, Chakraborty R, Coyne CB, Wrammert J, and Suthar MS
- Subjects
- Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Chorionic Villi, Cytokines genetics, Cytokines metabolism, Female, Gene Expression, Humans, Immunoglobulin G immunology, Infectious Disease Transmission, Vertical, Interferon Type I genetics, Interferon Type I metabolism, Macrophages virology, Pregnancy, Virus Internalization, Zika Virus, Antibodies, Viral immunology, Antibody-Dependent Enhancement immunology, Cross Reactions immunology, Dengue immunology, Dengue Virus immunology, Macrophages immunology, Placenta immunology, Zika Virus Infection immunology
- Abstract
Zika virus (ZIKV), which emerged in regions endemic to dengue virus (DENV), is vertically transmitted and results in adverse pregnancy outcomes. Antibodies to DENV can cross-react with ZIKV, but whether these antibodies influence ZIKV vertical transmission remains unclear. Here, we find that DENV antibodies increase ZIKV infection of placental macrophages (Hofbauer cells [HCs]) from 10% to over 80% and enhance infection of human placental explants. ZIKV-anti-DENV antibody complexes increase viral binding and entry into HCs but also result in blunted type I interferon, pro-inflammatory cytokine, and antiviral responses. Additionally, ZIKV infection of HCs and human placental explants is enhanced in an immunoglobulin G subclass-dependent manner, and targeting FcRn reduces ZIKV replication in human placental explants. Collectively, these findings support a role for pre-existing DENV antibodies in enhancement of ZIKV infection of select placental cell types and indicate that pre-existing immunity to DENV should be considered when addressing ZIKV vertical transmission., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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26. Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab.
- Author
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Cho A, Bradley B, Kauffman R, Priyamvada L, Kovalenkov Y, Feldman R, and Wrammert J
- Abstract
Rituximab is a therapeutic anti-CD20 monoclonal antibody widely used to treat B cell lymphoma and autoimmune diseases, such as rheumatic arthritis, systemic lupus erythematosus, and autoimmune blistering skin diseases (AIBD). While rituximab fully depletes peripheral blood B cells, it remains unclear whether some preexisting B cell memory to pathogens or vaccines may survive depletion, especially in lymphoid tissues, and if these memory B cells can undergo homeostatic expansion during recovery from depletion. The limited data available on vaccine efficacy in this setting have been derived from rituximab-treated patients receiving concomitant chemotherapy or other potent immunosuppressants. Here, we present an in-depth analysis of seasonal influenza vaccine responses in AIBD patients previously treated with rituximab, who generally did not receive additional therapeutic interventions. We found that, despite a lack of influenza-specific memory B cells in the blood, patients mount robust recall responses to vaccination, comparable to healthy controls, both at a cellular and a serological level. Repertoire analyses of plasmablast responses suggest that they likely derive from a diverse pool of tissue-resident memory cells, refractory to depletion. Overall, these data have important implications for establishing an effective vaccine schedule for AIBD patients and the clinical care of rituximab-treated patients in general and contribute to our basic understanding of maintenance of normal and pathogenic human B cell memory.
- Published
- 2017
- Full Text
- View/download PDF
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