Search

Your search keyword '"Rose, Rebecca"' showing total 1,200 results
Start Over Author "Rose, Rebecca"
1,200 results on '"Rose, Rebecca"'

2. HIV-1 subtypes maintain distinctive physicochemical signatures in Nef domains associated with immunoregulation.

Author

Lamers, Susanna, Fogel, Gary, Liu, Enoch, Nolan, David, Rose, Rebecca, and Mcgrath, Michael

Subjects
Bioinformatics, HIV, HIV subtypes, Machine-learning, Nef protein, Sequence analysis, Humans, HIV-1, Amino Acid Sequence, nef Gene Products, Human Immunodeficiency Virus, HIV Infections, Amino Acids, Disease Progression
Abstract

BACKGROUND: HIV subtype is associated with varied rates of disease progression. The HIV accessory protein, Nef, continues to be present during antiretroviral therapy (ART) where it has numerous immunoregulatory effects. In this study, we analyzed Nef sequences from HIV subtypes A1, B, C, and D using a machine learning approach that integrates functional amino acid information to identify if unique physicochemical features are associated with Nef functional/structural domains in a subtype-specific manner. METHODS: 2253 sequences representing subtypes A1, B, C, and D were aligned and domains with known functional properties were scored based on amino acid physicochemical properties. Following feature generation, we used statistical pruning and evolved neural networks (ENNs) to determine if we could successfully classify subtypes. Next, we used ENNs to identify the top five key Nef physicochemical features applied to specific immunoregulatory domains that differentiated subtypes. A signature pattern analysis was performed to the assess amino acid diversity in sub-domains that differentiated each subtype. RESULTS: In validation studies, ENNs successfully differentiated each subtype at A1 (87.2%), subtype B (89.5%), subtype C (91.7%), and subtype D (85.1%). Our feature-based domain scoring, followed by t-tests, and a similar ENN identified subtype-specific domain-associated features. Subtype A1 was associated with alterations in Nef CD4 binding domain; subtype B was associated with alterations with the AP-2 Binding domain; subtype C was associated with alterations in a structural Alpha Helix domain; and, subtype D was associated with alterations in a Beta-Sheet domain. CONCLUSIONS: Recent studies have focused on HIV Nef as a driver of immunoregulatory disease in those HIV infected and on ART. Nef acts through a complex mixture of interactions that are directly linked to the key features of the subtype-specific domains we identified with the ENN. The study supports the hypothesis that varied Nef subtypes contribute to subtype-specific disease progression.

Published
2023

5. Stroke in critically ill patients with respiratory failure due to COVID-19: Disparities between low-middle and high-income countries

Author

Al-Dabbous, Tala, Alfoudri, Huda, Shamsah, Mohammed, Alfroukh, Khadeejeh, Bairmani, Zinah Aqeel Abdulzahra, Khalid, Khalid Jehad, Abukhalaf, Salsabeel M.A., Hadhoud, Mohammed Maher, Abdrabo, Mohamed Fouad, Fathi, Mohamed, Alhouri, Hasan, Shahla, Dr Hamza, Alhadad, Qamrah, Hanan, Matly, Elapavaluru, Subbarao, Berg, Ashley, Horn, Christina, Abdelhalim, Ahmed Reda Mohamed Elsayed, Amer, Amro Essam, Elnaggar, Cinderella Omar Rageh, Hassan, Ahmed Ayman, Abdelaziz, Ali, Abdelhalim, Mohamed, Orabi, Yehia Samir Shaaban Aly, Alaraji, Zinah A., Muhaisen, Mo'nes R., Almasri, Lana, Mustafa, Dana, Hamdan, Shaher, Al-Saba'a, Yousef, Dalloul, Zaina, Alkahlout, Mohammed, Jaber, Hamza, Aldabbourosama, Osama, Abdalhadi, Alaa Abdalfattah, Hussein, Aliae AR Mohamed, Emad, Zarief Kamel, Khaled, Sarah, Mohamed, Nouralsabah, Hassanin, Ebtisam, Hamdi, Abdelhafeez, Gamal, May, Emad, Ahmed, Ragab, Abdelrahman, Azizeldin, Mohammed G, Hamza, Almthani, Omer, Alsarrah Ali Mohammed, Fadl alla, Asgad Osman Abdalla, Abdallahrs, Asia Atif Abdelrahman, Eltayeb, Aml Ahmed, Alhasan, Maali khalid mohamed abdalla, Abdelgaum, Esraa Hassan, Ahmed, Aya Mustafa, Abdulbaqi, Lamees Adil, Mohammedelhassan, Omer Abdullah, Ahmed, Musaab Mohammed Mohammed, Ali, Maha TagElser Mohammed, Mayasi, Yunis, Schroll, Stephan, Meyer, Dan, Velazco, Jorge, Ploskanych, Ludmyla, Fikes, Wanda, Bagewadi, Rohini, Dao, Marvin, White, Haley, Laviena, Alondra Berrios, Ehlers, Ashley, Shalabi-McGuire, Maysoon, Witt, Trent, Grazioli, Lorenzo, Lorini, Luca, Grandin, E. Wilson, Nunez, Jose, Reyes, Tiago, O'Briain, Diarmuid, Hunter, Stephanie, Ramanan, Mahesh, Affleck, Julia, Veerendra, Hemanth Hurkadli, Rai, Sumeet, Russell-Brown, Josie, Nourse, Mary, Joseph, Mark, Mitchell, Brook, Tenzer, Martha, Abe, Ryuzo, Cho, Hwa Jin, Jeong, In Seok, Rahman, Nadeem, Kakar, Vivek, Tamimi, Ahmed, Zabalawi, Diala, Elhennawi, Mohamed, Ghisulal, Praveen, Malik, Sadaf, Brozzi, Nicolas, Mehkri, Omar, Krishnan, Sudhir, Duggal, Abhijit, Houltham, Stuart, Graf, Jerónimo, Diaz, Roderigo, Orrego, Roderigo, Delgado, Camila, González, Joyce, Sanchez, Maria Soledad, Piagnerelli, Michael, Sarrazin, Josefa Valenzuela, Zabert, Prof. Gustavo, Espinosa, Lucio, Delgado, Paulo, Delgado, Victoria, Rincón, Diego Fernando Bautista, Yanten, Angela Maria Marulanda, Duque, Melissa Bustamante, Brodie, Daniel, Abouelmagd, Khaled, Elhazmi, Alyaa, Al-Hudaib, Abdullah, Javidfar, Jeff, Callahan, Maria, Dong, Andy, D'Orleans, Charles Crepy, Taufik, M. Azhari, Wardoyo, Elizabeth Yasmin, Gunawan, Margaretha, Trisnaningrum, Nurindah S, Irawany, Vera, Rayhan, Muhammad, Panigada, Mauro, Pesenti, Antonio, Zanella, Alberto, Grasselli, Giacomo, Colombo, Sebastiano, Martinet, Chiara, Florio, Gaetano, Antonelli, Massimo, Carelli, Simone, Grieco, Domenico L., Asaki, Motohiro, Hoshino, Kota, Salazar, Leonardo, Monsalve, Mary Alejandra Mendoza, Laffey, John, McNicholas, Bairbre, Cosgrave, David, Atif, Minha, Qutishat, Fadi, Laffey, Caoimhe, Van Der Walt, Michaeal, McCaffrey, Joseph, Bone, Allison, Trickey, Jemma, Horton, Michelle, Pearce, Stephanie, Salerno, Tania, Mohamed, Akram, Alhaddad, Salem, Bakeer, Baliad, Haitam, Shames, Shalabi, Laila, Ahmed, Mohammed Abodina, Hakeem, Yusuff, Winearls, James, Tallott, Mandy, Thomson, David, Joubert, Ivan, Arnold-Day, Christel, Piercy, Jenna, Smit, Richard van Zyl, Miller, Malcom, Seymour, Lisa, van Heyningen, Francois, Teyangesikayi, Gilbert, Fredericks, David, Hssain, Ali Ait, Aliudin, Jeffrey, Alqahtani, Al-Reem, Mohamed, Khoulod, Mohamed, Ahmed, Tan, Darwin, Villanueva, Joy, Zaqout, Ahmed, Labib, Ahmed, Kurtzman, Ethan, Ademi, Arben, Dobrita, Ana, Aoudi, Khadija El, Segura, Juliet, Giwangkancana, Gezy, Ohshimo, Shinichiro, Osatnik, Javier, Joosten, Anne, Torres, Antoni, Yang, Minlan, Motos, Ana, Luna, Carlos, Arancibia, Francisco, Williams, Virginie, Noel, Alexandre, Luque, Nestor, Fantini, Marina, García, Ruth Noemi Jorge, Alvarez, Enrique Chicote, Greti, Anna, Ceccato, Adrian, Sanchez, Angel, Vazquez, Ana Loza, Roche-Campo, Ferran, Franch-Llasat, Diego, Tuazon, Divina, Amato, Marcelo, Cassimiro, Luciana, Pola, Flavio, Ribeiro, Francis, Fonseca, Guilherme, Dalton, Heidi, Desai, Mehul, Osborn, Erik, Deeb, Hala, Arcadipane, Antonio, Martucci, Gennaro, Panarello, Giovanna, Vitiello, Stefano, Bianco, Claudia, Occhipinti, Giovanna, Rossetti, Matteo, Cuffaro, Raffaele, Siddig, Nidhal, Cho, Sung-Min, Whitman, Glenn, Sayed, Marwan El, Mokhtar, Walaa, El-Shenawy, Eslam, Shimizu, Hiroaki, Moriyama, Naoki, Kim, Jae-Burm, Kitamura, Nobuya, Gebauer, Johannes, Yokoyama, Toshiki, Al-Fares, Abdulrahman, Buabbas, Sarah, Alamad, Esam, Alawadhi, Fatma, Alawadi, Kalthoum, Khalefa, Mohamed Ahmed, Ajeel, Nourah Ahmad Abdulaziz Al, Aly, Mohammad Fathy, Al-Saleh, Abdullah, Naanouh, Abdullah, Elshourbgy, Alaa Mohammed, Gad, Mohamed Yousef, ElRazaz, Rania Mohamed, Khadadah, Ibrahim, Almumin, Ahmed Mohammed, Altarakma, Hala, Albannay, Hasan, Alsaleh, Mohammed Kh, Radwan, Mahmoud Saad Abdallah, Saadallah, Islam Ahmed, Tanaka, Hiro, Hashimoto, Satoru, Yamazaki, Masaki, Oh, Tak-Hyuck, Epler, Mark, Forney, Cathleen, Kruse, Louise, Feister, Jared, Williamson, Joelle, Grobengieser, Katherine, Gnall, Eric, Golden, Sasha, Caroline, Mara, Shapiro, Timothy, Karaj, Colleen, Thome, Lisa, Sher, Lynn, Vanderland, Mark, Welch, Mary, McDermott, Sherry, Brain, Matthew, Mineall, Sarah, Unwin, Maria, Chen, Lixian, Trezise, Tarnya, McKeon, Laurie, Kimura, Dai, Brazzi, Luca, Sales, Gabriele, Montrucchio, Giorgia, Ogston, Tawnya, Nagpal, Dave, Fischer, Karlee, Lorusso, Roberto, van Bussell, Bas, De Piero, Maria Elena, Mariani, Silvia, Rangappa, Dr Rajavardhan, Shetty, Dr Rajesh Mohan, P, Sujin Rai, Ganesan, Argin, Tharwat, Samar, Esperatti, Mariano, Fuentes, Nora Angélica, Gonzalez, Maria Eugenia, Carton, Edmund G., Sen, Ayan, Palacios, Amanda, Rainey, Deborah, Samoukoviv, Gordan, Campisi, Josie, Durham, Lucia, Neumann, Emily, Seefeldt, Cassandra, Falcucci, Octavio, Emmrich, Amanda, Guy, Jennifer, Johns, Carling, Potzner, Kelly, Zimmermann, Catherine, Espinal, Angelia, Buchtele, Nina, Schwameis, Michael, Korhnfehl, Andrea, Brock, Roman, Staudinger, Thomas, Stecher, Stephanie-Susanne, Barnikel, Michaela, Antón, Sófia, Pawlikowski, Alexandra, Zaaqoq, Akram, Galloway, Lan Anh, Merley, Caitlin, Muftah, Mohamed, Nichol, Alistair, Csete, Marc, Quesada, Luisa, Saba, Isabela, Kasugai, Daisuke, Hiraiwa, Hiroaki, Tanaka, Taku, Marwali, Eva, Purnama, Yoel, Dewayanti, Santi Rahayu, Ardiyan, Juzar, Dafsah Arifa, Siagian, Debby, Chen, Yih-Sharng, Aldhalia, Amer, Ogino, Mark, Nasa, Prashant, Matthew, Christina, Majeed, Nimisha Abdul, Hafez, Wael, Ratsep, Indrek, Post, Andra-Maris, Sillaots, Piret, Krund, Anneli, Lehiste, Merili-Helen, Lepik, Tanel, Manetta, Frank, Mihelis, Effe, Sarmiento, Iam Claire, Narasimhan, Mangala, Varrone, Michael, Komats, Mamoru, Garcia-Diaz, Julia, Harmon, Catherine, Satyapriya, S. Veena, Bhatt, Amar, Mokadam, Nahush A., Uribe, Alberto, Gonzalez, Alicia, Shi, Haixia, McKeown, Johnny, Pasek, Joshua, Fiorda, Juan, Echeverria, Marco, Moreno, Rita, Zakhary, Bishoy, Cavana, Marco, Cucino, Alberto, Foti, Giuseppe, Giani, Marco, Fumagalli, Benedetta, Chiumello, Davide, Castagna, Valentina, Dell'Amore, Andrea, Navalesi, Paolo, Shum, Hoi-Ping, Vuysteke, Alain, Usman, Asad, Acker, Andrew, Smood, Benjamin, Mergler, Blake, Sertic, Federico, Subramanian, Madhu, Sperry, Alexandra, Rizer, Nicolas, Burhan, Erlina, Rasmin, Menaldi, Akmal, Ernita, Sitompul, Faya, Lolong, Navy, Naivedh, Bhat, Erickson, Simon, Barrett, Peter, Dean, David, Daugherty, Julia, Loforte, Antonio, Khan, Irfan, Quraishi, Mohammed Abraar, DeSantis, Olivia, Nasrallah, Ahmad, So, Dominic, Kandamby, Darshana, Mandei, Jose M., Natanael, Hans, YudhaLantang, Eka, Lantang, Anastasia, Wijaya, Surya Oto, Jung, Anna, Ng, George, Ng, Wing Yiu, Ng, Pauline Yeung, Fang, Shu, Tabah, Alexis, Ratcliffe, Megan, Duroux, Maree, Alajeeli, Ahmed, Tarhabat, Ali, Adachi, Shingo, Nakao, Shota, Blanco, Pablo, Prieto, Ana, Sánchez, Jesús, Nicholson, Meghan, Butt, Warwick, Serratore, Alyssa, Delzoppo, Carmel, Janin, Pierre, Yarad, Elizabeth, Totaro, Richard, Coles, Jennifer, Pujo, Bambang, Balk, Robert, Vissing, Andy, Kapania, Esha, Hays, James, Fox, Samuel, Yantosh, Garrett, Mishin, Pavel, Adem, Safia, Yuliarto, Saptadi, Santoso, Kohar Hari, Djajalaksana, Susanthy, Fatoni, Arie Zainul, Fukuda, Masahiro, Liu, Keibun, Pelosi, Paolo, Battaglini, Denise, Robba, Chiara, Jiménez, Juan Fernando Masa, Bastos, Diego, Gaião, Sérgio, Rusmawatiningtyas, Desy, Cho, Young-Jae, Lee, Su Hwan, Kawasaki, Tatsuya, Munshi, Laveena, Sakiyalak, Pranya, Nitayavardhana, Prompak, Elagili, Mohamed Bashir, Salem, Talat Ahmed Abu, Seitz, Tamara, Arora, Rakesh, Kent, David, Marino, Daniel, Parwar, Swapnil, Cheng, Andrew, Miller, Jennene, Fujitani, Shigeki, Shimizu, Naoki, Madhok, Jai, Owyang, Clark, Buscher, Hergen, Reynolds, Claire, Abdurraouf, Abusalama, Kredan, Ali Abdulnasir, Haddud, Abdurrahman, Moharam, Saad, Maasikas, Olavi, Beljantsev, Aleksan, Mihnovits, Vladislav, Akimoto, Takako, Aizawa, Mariko, Horibe, Kanako, Onodera, Ryota, Hodgson, Carol, Burrell, Aidan, Young, Meredith, George, Timothy, Shekar, Kiran, McGuinness, Niki, Irvine, Lacey, Flynn, Brigid, Almjersah, Abdulrahman, Bakri, Ashraf, Endo, Tomoyuki, Sugiyama, Kazuhiro, Shimizu, Keiki, Fan, Eddy, Exconde, Kathleen, Ichiba, Shingo, Binnawara, Muhannud, Embarek, Hussein, Lussier, Leslie, Lotz, Gösta, Malfertheiner, Maximilian, Maier, Lars, Dreier, Esther, Kusumastuti, Neurinda Permata, McCloskey, Colin, Dabaliz, Al-Awwab, Elshazly, Tarek B, Smith, Josiah, Szuldrzynski, Konstanty S., Bielański, Piotr, Wille, Keith, Murthy, Srinivas, Parhar, Ken Kuljit S., Fiest, Kirsten M., Codan, Cassidy, Shahid, Anmol, Fayed, Mohamed, Evans, Timothy, Garcia, Rebekah, Gutierrez, Ashley, Song, Tae, Rose, Rebecca, Bennett, Suzanne, Richardson, Denise, Peek, Giles, Arora, Lovkesh, Rappapport, Kristina, Rudolph, Kristina, Sibenaller, Zita, Stout, Lori, Walter, Alicia, Herr, Daniel, Vedadi, Nazli, Bartlett, Robert, Thompson, Shaun, Hoffman, Julie, Ying, Xiaonan, Williams, Bailey, Sanchez, Emely, Akwani, Chika, Kennedy, Ryan, Elhadi, Muhammed, Griffee, Matthew, Mone, Mary, Ciullo, Anna, Kida, Yuri, Roca, Ricard Ferrer, Riera, JordI, Contreras, Sofia, Alegre, Cynthia, Kay, Christy, Fischer, Irene, Renner, Elizabeth, Taniguci, Hayato, Lee, James, Plotkin, Daniel, Citarella, Barbara Wanjiru, Merson, Laura, Hartley, Emma, Lubis, Bastian, Ikeyama, Takanari, Mortada, Alshaymaa, Alhamad, Ameen, Mechi, Ahmed, Nadar, Islam Mohsen Ali Mohamed Hassan, Alyasiri, Mohammed Saleh, Elsaid, Muhammed Zainab Alghali, Bhaskar, Balu, Jung, Jae-Seung, McGuinness, Shay, Eastwood, Glenn, Marta, Sandra Rossi, Guarracino, Fabio, Gerle, Stacy, Coxon, Emily, Claro, Bruno, Aldressi, Wafa, Eleisawy, Mahmoud, Osama, Hasnaa, Loverde, Daniel, Patil, Namrata, Parrini, Vieri, McBride, Angela, Negaard, Kathryn, Ratsch, Angela, Abdelaziz, Ahmad, Uribe, Juan David, Peris, Adriano, Sanders, Mark, Emerson, Dominic, Kamal, Muhammad, Faida, Hamza, Povoa, Pedro, Francis, Roland, Cherif, Ali, Joseph, Sunimol, Nardo, Matteo Di, Heard, Micheal, Kyle, Kimberly, Blackwell, Ray A, OUYAHIA, Amel, Biston, Patrick, Jeong, Hye Won, Smith, Reanna, Prawira, Yogi, Garcia, Arturo Huerta, Salterain, Nahikari, Meyns, Bart, Elnasser, Muhammed, Moreno, Marsha, Walia, Rajat, Mehta, Amit, Schweda, Annette, Williams, Melissa, Amkhatirah, Emad, Kim, Kyung Hoon, Assad, Alexandra, Giraldo, Estefania, Karolak, Wojtek, Balik, Martin, Pocock, Elizabeth, Gajkowski, Evan, Bedair, Mohamed, Masafumi, Kanamoto, Barrett, Nicholas, Takeyama, Yoshihiro, Park, Sunghoon, Amin, Faizan, Andriyani, Fina Meilyana, Sudakevych, Serhii, Schnur, Janos, Vera, Magdalena, Cornejo, Rodrigo, Schwarz, Patrícia, Mardini, Ana Carolina, de Paula, Thais, Neto, Ary Serpa, Villoldo, Andrea, Colafranceschi, Alexandre Siciliano, Iglesias, Alejandro Ubeda, Granjean, Juan, Melro, Lívia Maria Garcia, Romualdo, Giovana Fioravante, Gaia, Diego, Souza, Helmgton, Galas, Filomena, Mendiluce, Rafael Máñez, Sosa, Alejandra, Martinez, Ignacio, Kurosawa, Hiroshi, Almoshantaf, Mohammad Badr, Salgado, Juan, Hugi-Mayr, Beate, Charbonneau, Eric, Barzilai, Vitor Salvatore, Monteiro, Veronica, de Souza, Rodrigo Ribeiro, Harper, Michael, Suzuki, Hiroyuki, Adams, Celina, Brieva, Jorge, Khamees, Almu'atasim, Graige, Fadi, Supriatna, Moh, Nyale, George, Eltatar, Faisal Saleem, Fatani, Jihan, Baeissa, Husam, Masri, Ayman AL, Rabie, Ahmed, Hui, Mok Yee, Yamane, Masahiro, Jung, Hanna, Margaret, Ayorinde Mojisola, Nacpil, Newell, Ruck, Katja, Bakken, Rhonda, Jara, Claire, Felton, Tim, Berra, Lorenzo, Shah, Bobby, Chakraborty, Arpan, Cardona, Monika, Capatos, Gerry, Akkanti, Bindu, Orija, Abiodun, Jain, Harsh, Ito, Asami, Housni, Brahim, Low, Sennen, Iihara, Koji, Chavez, Joselito, Ramanathan, Kollengode, Zabert, Gustavo, Naidoo, Krubin, Seppelt, Ian, VanDyk, Marlice, MacDonald, Sarah, McGregor, Randy, Siebenaler, Teka, Flynn, Hannah, Lofton, Kristi, Aokage, Toshiyuki, Kvirkvelia, Bakar, Shigemitsu, Kazuaki, Moscatelli, Andrea, Fiorentino, Giuseppe, Baumgaertel, Matthias, Mba, Serge Eddy, Assy, Jana, Hutahaean, Amelya, Roush, Holly, Sichting, Kay A, Alessandri, Francesco, Burns, Debra, Alkhubouli, Taha Husayn, Salt, Gavin, Garabedian, Carl P., Millar, Jonathan, Sim, Malcolm, Mattke, Adrian, McAuley, Danny, Tadili, Jawad, Frenzel, Tim, Abuleil, Amro, Bar-Lavie, Yaron, Ortiz, Aaron Blandino, Stone, Jackie, Attokaran, Antony, Farquharson, Michael, Patel, Brij, Gunning, Derek, Baillie, Kenneth, Watson, Pia, Tamai, Kenji, Saaid, Ayoub, Anania, Pasquale, Sajinadiyasa, Gede Ketut, Kanyawati, Dyah, Salgado, Marcello, Sassine, Assad, Yudo, Bhirowo, McCaul, Scott, Lee, Bongjin, Lee, Sang Min, Afek, Arnon, Fattouh, Shimaa E, Iwashita, Yoshiaki, Fadlalmola, Hammad, Semedi, Bambang Pujo, Mansour, Noureldin Mohamed, Metiva, Jack, Van Belle, Nicole, Martin-Loeches, Ignacio, Al-Sadawi, Dr Mohammed, Kirakli, Cenk, Shimaa, Al-Touny, Ivatt, Lenny, Woon, Chia Yew, Kang, Hyun Mi, Smith, Timothy, James, Erskine, Al-Rawas, Nawar, Iwasaki, Yudai, Ashour, Hamza, King-Chung, Kenny Chan, Gudzenko, Vadim, Taccone, Fabio, Perdhana, Fajar, Lamarche, Yoan, Ribeiro, Joao Miguel, Bradic, Nikola, Van den Bossche, Klaartje, Lansink, Oude, Singh, Gurmeet, Debeuckelaere, Gerdy, Stelfox, Henry T., Yi, Cassia, Elia, Jennifer, Tribble, Thomas, Shankar, Shyam, Padmanabhan, Raj, Hallinan, Bill, Paoletti, Luca, Leyva, Yolanda, Fykuda, Tatuma, Badulak, Jenelle, Koch, Jillian, Janowaik, Lisa, Hackman, Amy, Hernandez, Deb, Osofsky, Jennifer, Donadello, Katia, Lawang, Aizah, Fine, Josh, Davidson, Benjamin, Vazquez, Andres Oswaldo Razo, Abdehaleem, Ibrahim, Kelly, Thu-Lan, Fanning, Jonathon, Premraj, Lavienraj, Porto, Diego Bastos, White, Nicole M., Bassi, Gianluigi Li, Suen, Jacky, and Fraser, John F.

Published
2024
Full Text
View/download PDF

8. Temporary increase in circulating replication-competent latent HIV-infected resting CD4+ T cells after switch to an integrase inhibitor based antiretroviral regimen

Author

Ferreira, Roux-Cil, Reynolds, Steven J., Capoferri, Adam A., Baker, Owen R., Brown, Erin E., Klock, Ethan, Miller, Jernelle, Lai, Jun, Saraf, Sharada, Kirby, Charles, Lynch, Briana, Hackman, Jada, Gowanlock, Sarah N., Tomusange, Stephen, Jamiru, Samiri, Anok, Aggrey, Kityamuweesi, Taddeo, Buule, Paul, Bruno, Daniel, Martens, Craig, Rose, Rebecca, Lamers, Susanna L., Galiwango, Ronald M., Poon, Art F.Y., Quinn, Thomas C., Prodger, Jessica L., and Redd, Andrew D.

Published
2024
Full Text
View/download PDF

10. The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi’s Sarcoma Tumors during Antiretroviral Therapy

Author

Nolan, David J, Rose, Rebecca, Zhang, Rongzhen, Leong, Alan, Fogel, Gary B, Scholte, Larissa LS, Bethony, Jeffrey M, Bracci, Paige, Lamers, Susanna L, and McGrath, Michael S

Subjects
Microbiology, Biological Sciences, Genetics, Rare Diseases, HIV/AIDS, Infectious Diseases, Cancer, Aetiology, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Humans, Gene Products, nef, Herpesvirus 8, Human, HIV, HIV Infections, Leukocytes, Mononuclear, nef Gene Products, Human Immunodeficiency Virus, RNA, Sarcoma, Kaposi, Tumor Microenvironment, HIV Nef, viral reservoirs, Kaposi's sarcoma, HIV transcription, Kaposi’s sarcoma
Abstract

Epidemic Kaposi's sarcoma (KS), defined by co-infection with Human Herpes Virus 8 (HHV-8) and the Human Immunodeficiency Virus (HIV), is a major cause of mortality in sub-Saharan Africa. Antiretroviral therapy (ART) significantly reduces the risk of developing KS, and for those with KS, tumors frequently resolve with ART alone. However, for unknown reasons, a significant number of KS cases do not resolve and can progress to death. To explore how HIV responds to ART in the KS tumor microenvironment, we sequenced HIV env-nef found in DNA and RNA isolated from plasma, peripheral blood mononuclear cells, and tumor biopsies, before and after ART, in four Ugandan study participants who had unresponsive or progressive KS after 180-250 days of ART. We performed immunohistochemistry experiments to detect viral proteins in matched formalin-fixed tumor biopsies. Our sequencing results showed that HIV diversity and RNA expression in KS tumors are maintained after ART, despite undetectable plasma viral loads. The presence of spliced HIV transcripts in KS tumors after ART was consistent with a transcriptionally active viral reservoir. Immunohistochemistry staining found colocalization of HIV Nef protein and tissue-resident macrophages in the KS tumors. Overall, our results demonstrated that even after ART reduced plasma HIV viral load to undetectable levels and restored immune function, HIV in KS tumors continues to be transcriptionally and translationally active, which could influence tumor maintenance and progression.

Published
2022

14. Emergence of an early SARS-CoV-2 epidemic in the United States.

Author

Zeller, Mark, Gangavarapu, Karthik, Anderson, Catelyn, Smither, Allison R, Vanchiere, John A, Rose, Rebecca, Snyder, Daniel J, Dudas, Gytis, Watts, Alexander, Matteson, Nathaniel L, Robles-Sikisaka, Refugio, Marshall, Maximilian, Feehan, Amy K, Sabino-Santos, Gilberto, Bell-Kareem, Antoinette R, Hughes, Laura D, Alkuzweny, Manar, Snarski, Patricia, Garcia-Diaz, Julia, Scott, Rona S, Melnik, Lilia I, Klitting, Raphaëlle, McGraw, Michelle, Belda-Ferre, Pedro, DeHoff, Peter, Sathe, Shashank, Marotz, Clarisse, Grubaugh, Nathan D, Nolan, David J, Drouin, Arnaud C, Genemaras, Kaylynn J, Chao, Karissa, Topol, Sarah, Spencer, Emily, Nicholson, Laura, Aigner, Stefan, Yeo, Gene W, Farnaes, Lauge, Hobbs, Charlotte A, Laurent, Louise C, Knight, Rob, Hodcroft, Emma B, Khan, Kamran, Fusco, Dahlene N, Cooper, Vaughn S, Lemey, Phillipe, Gardner, Lauren, Lamers, Susanna L, Kamil, Jeremy P, Garry, Robert F, Suchard, Marc A, and Andersen, Kristian G

Subjects
Humans, Risk Factors, Disease Outbreaks, Phylogeny, Travel, United States, Louisiana, Texas, Databases as Topic, Epidemics, COVID-19, SARS-CoV-2, genomic epidemiology, mobility, phylogenetics, viral emergence, viral sequencing, Emerging Infectious Diseases, Biodefense, Prevention, Vaccine Related, Lung, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.

Published
2021

20. Integrated proteomics and genomics analysis of paradoxical eczema in psoriasis patients treated with biologics

Author

Ahmed, Shehnaz, Alabas, Oras, Barker, Jonathan, Becher, Gabrielle, Bewley, Anthony, Evans, Ian, Hampton, Philip, Kirby, Brian, Kleyn, Elise, Laws, Philip, Lawson, Linda, Mackenzie, Teena, McElhone, Kathleen, McPherson, Tess, Morrison, Simon, Owen, Caroline, Pearson, Eleanor, Rashid, Amir, Reynolds, Nick, Strangfeld, Anja, Walton, Shernaz, Yiu, Zenas, Gupta, Girish, Strangfeld (chair), Anja, Weller, Richard, Zietemann, Vera, Aldoori, Nadia, Ali, Mahmud, Al-Rusan, Ahmed, Angit, Caroline, Anstey, Alex, Antony, Fiona, Archer, Charles, August, Suzanna, Balasubramaniam, Periasamy, Baudry, David, Baxter, Kay, Bonsall, Alexandra, Brown, Sara, Brown, Victoria, Burden, David, Burova, Ekaterina, Butt, Aamir, Caswell, Mel, Chapman, Anna, Cliff, Sandeep, Costache, Mihaela, Darne, Sharmela, DeGiovanni, Claudia, Desai, Trupti, Diba, Victoria, Domanne, Eva, Duckworth, Michael, Dymond, Harvey, Fahy, Caoimhe, Farwer, Susanne, Ferguson, Leila, Gkini, Maria-Angeliki, Godwin, Alison, Goulding, Jon, Hammonds, Fiona, Haque, Shaheen, Higgins, Caroline, Hood, Sue, Joseph, Teresa, Johnson, Sarah, Kalavala, Manju, Khorshid, Mohsen, Labinoti, Liberta, Lamb, Ruth, Lawson, Nicole, Layton, Alison, Lees, Tara, Levell, Nick, Lewis, Helen, Lovell, Chris, Lyon, Calum, McAteer, Helen, McBride, Sandy, McCormack, Sally, McKenna, Kevin, Mellor, Serap, Meredith, Fiona, Murphy, Ruth, Norris, Paul, Parslew, Richard, Perera, Gay, Ponnambath, Nabil, Popli, Urvi, Powell, James, Ramesh, Raakhee, Ramsay, Helen, Ranasinghe, Aruni, Reeken, Saskia, Rose, Rebecca, Rotarescu, Rada, Salvary, Ingrid, Sands, Kathy, Sinha, Tapati, Schofield, Julia, Shipman, Alexa, Siebert, Stefan, Stefanescu, Simina, Sundararaj, Kavitha, Taghipour, Kathy, Taylor, Michelle, Thomson, Michelle, Topliffe, Joanne, Verdolini, Roberto, Wachsmuth, Rachel, Wade, Martin, Wahie, Shymal, Walsh, Sarah, Wilcox, Louise, Williamson, Diane, Wright, Andrew, Al-Janabi, Ali, Martin, Paul, Khan, Adnan R., Foulkes, Amy C., Smith, Catherine H., Griffiths, Christopher E.M., Morris, Andrew P., Eyre, Steve, and Warren, Richard B.

Published
2023
Full Text
View/download PDF

22. Distinct rates and patterns of spread of the major HIV-1 subtypes in Central and East Africa.

Author

Faria, Nuno R, Vidal, Nicole, Lourenco, José, Raghwani, Jayna, Sigaloff, Kim CE, Tatem, Andy J, van de Vijver, David AM, Pineda-Peña, Andrea-Clemencia, Rose, Rebecca, Wallis, Carole L, Ahuka-Mundeke, Steve, Muyembe-Tamfum, Jean-Jacques, Muwonga, Jérémie, Suchard, Marc A, Rinke de Wit, Tobias F, Hamers, Raph L, Ndembi, Nicaise, Baele, Guy, Peeters, Martine, Pybus, Oliver G, Lemey, Philippe, and Dellicour, Simon

Subjects
Humans, HIV-1, HIV Infections, Africa, Central, Africa, Eastern, Africa, Central, Eastern, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

Since the ignition of the HIV-1 group M pandemic in the beginning of the 20th century, group M lineages have spread heterogeneously throughout the world. Subtype C spread rapidly through sub-Saharan Africa and is currently the dominant HIV lineage worldwide. Yet the epidemiological and evolutionary circumstances that contributed to its epidemiological expansion remain poorly understood. Here, we analyse 346 novel pol sequences from the DRC to compare the evolutionary dynamics of the main HIV-1 lineages, subtypes A1, C and D. Our results place the origins of subtype C in the 1950s in Mbuji-Mayi, the mining city of southern DRC, while subtypes A1 and D emerged in the capital city of Kinshasa, and subtypes H and J in the less accessible port city of Matadi. Following a 15-year period of local transmission in southern DRC, we find that subtype C spread at least three-fold faster than other subtypes circulating in Central and East Africa. In conclusion, our results shed light on the origins of HIV-1 main lineages and suggest that socio-historical rather than evolutionary factors may have determined the epidemiological fate of subtype C in sub-Saharan Africa.

Published
2019

24. Emerging Patterns in HIV-1 gp120 Variable Domains in Anatomical Tissues in the Absence of a Plasma Viral Load

Author

Lamers, Susanna L, Fogel, Gary B, Nolan, David J, Barbier, Andrew E, Rose, Rebecca, Singer, Elyse J, Gonzalez-Perez, Maria Paz, and McGrath, Michael S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Infection, Anti-HIV Agents, Autopsy, Disease Reservoirs, HIV Envelope Protein gp120, HIV Infections, HIV-1, Humans, Peptide Fragments, Sequence Analysis, DNA, Viral Load, HIV envelope, tissue-based reservoirs, envelope diversity, Clinical Sciences, Virology, Clinical sciences
Abstract

The HIV envelope protein contains five hypervariable domains (V1-V5) that are fundamental for cell entry. We contrasted modifications in the variable domains derived from a panel of 24 tissues from 7 subjects with no measurable plasma viral load (NPVL) to variable domains from 76 tissues from 15 subjects who had a detectable plasma viral load (PVL) at death. NPVL subject's V1 and V2 domains were usually highly length variable, whereas length variation in PVL sequences was more conserved. Longer V1s contained more charged residues, whereas longer V2s were more glycosylated. Structural analysis demonstrated V1/V2 charge, and N-site additions/subtractions were localized to the CD4 binding pocket. Diversified envelopes in tissues during therapy may represent a mechanism for HIV persistence in tissues, as binding pocket complexity is associated with HIV that may escape neutralization, whereas shorter envelopes are associated with increased infectivity. Further analysis of tissue-derived envelope sequences may enable better understanding of potential immunological approaches targeting the persistent HIV reservoir.

Published
2019

25. Differences in Clinical Features and Comorbid Burden between HLA-C∗06:02 Carrier Groups in >9,000 People with Psoriasis

Author

Evans, Ian, Murphy, Ruth, McPherson, Tess, Kleyn, Elise, Laws, Philip, Becher, Gabrielle, Bewley, Anthony, Rashid, Amir, Alabas, Oras, Morrison, Simon, Ahmed, Shehnaz, Pearson, Eleanor, Richards, Josh, Mackenzie, Teena, Kirby, Brian, Burden, David, Lawson, Linda, McElhone, Kathleen, Ormerod, Anthony, Owen, Caroline, Aldoori, Nadia, Ali, Mahmud, Anstey, Alex, Antony, Fiona, Archer, Charles, August, Suzanna, Balasubramaniam, Periasamy, Baxter, Kay, Bonsall, Alexandra, Brown, Victoria, Burova, Katya, Butt, Aamir, Caswell, Mel, Cliff, Sandeep, Costache, Mihaela, Darne, Sharmela, Davies, Emily, DeGiovanni, Claudia, Desai, Trupti, DeSilva, Bernadette, Diba, Victoria, Domanne, Eva, Dymond, Harvey, Fahy, Caoimhe, Ferguson, Leila, Gkini, Maria-Angeliki, Godwin, Alison, Hammonds, Fiona, Johnson, Sarah, Joseph, Teresa, Kalavala, Manju, Khorshid, Mohsen, Labinoti, Liberta, Lawson, Nicole, Layton, Alison, Lees, Tara, Levell, Nick, Lewis, Helen, Lyon, Calum, McBride, Sandy, McCormack, Sally, McKenna, Kevin, Mellor, Serap, Norris, Paul, Popli, Urvi, Perera, Gay, Ponnambath, Nabil, Ramsay, Helen, Ranasinghe, Aruni, Reeken, Saskia, Rose, Rebecca, Rotarescu, Rada, Salvary, Ingrid, Sands, Kathy, Sinha, Tapati, Stefanescu, Simina, Sundararaj, Kavitha, Taghipour, Kathy, Taylor, Michelle, Thomson, Michelle, Topliffe, Joanne, Verdolini, Roberto, Wachsmuth, Rachel, Wade, Martin, Wahie, Shyamal, Walsh, Sarah, Walton, Shernaz, Wilcox, Louise, Wright, Andrew, Douroudis, Konstantinos, Ramessur, Ravi, Barbosa, Ines A., Baudry, David, Duckworth, Michael, Angit, Caroline, Capon, Francesca, Chung, Raymond, Curtis, Charles J., Di Meglio, Paola, Goulding, Jonathan M.R., Griffiths, Christopher E.M., Lee, Sang Hyuck, Mahil, Satveer K., Parslew, Richard, Reynolds, Nick J., Shipman, Alexa R., Warren, Richard B., Yiu, Zenas Z.N., Simpson, Michael A., Barker, Jonathan N., Dand, Nick, and Smith, Catherine H.

Published
2022
Full Text
View/download PDF

26. Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study

Author

Fanning, Jonathon P., Weaver, Natasha, Fanning, Robert B., Griffee, Matthew J., Cho, Sung-Min, Panigada, Mauro, Obonyo, Nchafatso G., Zaaqoq, Akram M., Rando, Hannah, Chia, Yew Woon, Fan, Bingwen Eugene, Sela, Declan, Chiumello, Davide, Coppola, Silvia, Labib, Ahmed, Whitman, Glenn J. R., Arora, Rakesh C., Kim, Bo S., Motos, Anna, Torres, Antoni, Barbé, Ferran, Grasselli, Giacomo, Zanella, Alberto, Etchill, Eric, Usman, Asad Ali, Feth, Maximilian, White, Nicole M., Suen, Jacky Y., Li Bassi, Gianluigi, Peek, Giles J., Fraser, John F., Dalton, Heidi, Al-Dabbous, Tala, Alfoudri, Huda, Shamsah, Mohammed, Elapavaluru, Subbarao, Berg, Ashley, Horn, Christina, Mayasi, Yunis, Schroll, Stephan, Meyer, Dan, Velazco, Jorge, Ploskanych, Ludmyla, Fikes, Wanda, Bagewadi, Rohini, Dao, Marvin, White, Haley, Berrios Laviena, Alondra, Ehlers, Ashley, Shalabi-McGuire, Maysoon, Witt, Trent, Grazioli, Lorenzo, Lorini, Luca, Wilson Grandin, E., Nunez, Jose, Reyes, Tiago, O’Briain, Diarmuid, Hunter, Stephanie, Ramanan, Mahesh, Affleck, Julia, Hurkadli Veerendra, Hemanth, Rai, Sumeet, Russell-Brown, Josie, Nourse, Mary, Joseph, Mark, Mitchell, Brook, Tenzer, Martha, Abe, Ryuzo, Jin Cho, Hwa, Seok Jeong, In, Rahman, Nadeem, Kakar, Vivek, Brozzi, Nicolas, Mehkri, Omar, Krishnan, Sudhir, Duggal, Abhijit, Houltham, Stuart, Graf, Jerónimo, Diaz, Roderigo, Orrego, Roderigo, Delgado, Camila, González, Joyce, Soledad Sanchez, Maria, Piagnerelli, Michael, Valenzuela Sarrazin, Josefa, Zabert, Gustavo, Espinosa, Lucio, Delgado, Paulo, Delgado, Victoria, Rincón, Diego Fernando Bautista, Yanten, Angela Maria Marulanda, Bustamante Duque, Melissa, Brodie, Daniel, Elhazmi, Alyaa, Al-Hudaib, Abdullah, Callahan, Maria, Azhari Taufik, M., Yasmin Wardoyo, Elizabeth, Gunawan, Margaretha, Trisnaningrum, Nurindah S, Irawany, Vera, Rayhan, Muhammad, Panigada, Mauro, Pesenti, Antonio, Zanella, Alberto, Grasselli, Giacomo, Colombo, Sebastiano, Martinet, Chiara, Florio, Gaetano, Antonelli, Massimo, Carelli, Simone, Grieco, Domenico L., Asaki, Motohiro, Hoshino, Kota, Salazar, Leonardo, Monsalve, Mary Alejandra Mendoza, Laffey, John, McNicholas, Bairbre, Cosgrave, David, McCaffrey, Joseph, Bone, Allison, Hakeem, Yusuff, Winearls, James, Tallott, Mandy, Thomson, David, Arnold-Day, Christel, Cupido, Jerome, Fanie, Zainap, Miller, Malcom, Seymore, Lisa, van Straaten, Dawid, Ait Hssain, Ali, Aliudin, Jeffrey, Alqahtani, Al-Reem, Mohamed, Khoulod, Mohamed, Ahmed, Tan, Darwin, Villanueva, Joy, Zaqout, Ahmed, Kurtzman, Ethan, Ademi, Arben, Dobrita, Ana, El Aoudi, Khadija, Segura, Juliet, Giwangkancana, Gezy, Ohshimo, Shinichiro, Osatnik, Javier, Joosten, Anne, Torres, Antoni, Yang, Minlan, Motos, Ana, Luna, Carlos, Arancibia, Francisco, Williams, Virginie, Noel, Alexandre, Luque, Nestor, Fantini, Marina, García, Ruth Noemi Jorge, Chicote Alvarez, Enrique, Greti, Anna, Ceccato, Adrian, Sanchez, Angel, Loza Vazquez, Ana, Roche-Campo, Ferran, Franch-Llasat, Diego, Tuazon, Divina, Amato, Marcelo, Cassimiro, Luciana, Pola, Flavio, Ribeiro, Francis, Fonseca, Guilherme, Dalton, Heidi, Desai, Mehul, Osborn, Erik, Deeb, Hala, Arcadipane, Antonio, Martucci, Gennaro, Panarello, Giovanna, Vitiello, Chiara, Bianco, Claudia, Occhipinti, Giovanna, Rossetti, Matteo, Cuffaro, Raffaele, Cho, Sung-Min, Whitman, Glenn, Shimizu, Hiroaki, Moriyama, Naoki, Kim, Jae-Burm, Kitamura, Nobuya, Gebauer, Johannes, Yokoyama, Toshiki, Al-Fares, Abdulrahman, Buabbas, Sarah, Alamad, Esam, Alawadhi, Fatma, Alawadi, Kalthoum, Tanaka, Hiro, Hashimoto, Satoru, Yamazaki, Masaki, Oh, Tak-Hyuck, Epler, Mark, Forney, Cathleen, Kruse, Louise, Feister, Jared, Williamson, Joelle, Grobengieser, Katherine, Gnall, Eric, Golden, Sasha, Caroline, Mara, Shapiro, Timothy, Karaj, Colleen, Thome, Lisa, Sher, Lynn, Vanderland, Mark, Welch, Mary, McDermott, Sherry, Brain, Matthew, Mineall, Sarah, Kimura, Dai, Brazzi, Luca, Sales, Gabriele, Montrucchio, Giorgia, Ogston, Tawnya, Nagpal, Dave, Fischer, Karlee, Lorusso, Roberto, Rangappa, Rajavardhan, Rai, Sujin, Appu, Argin, Esperatti, Mariano, Angélica Fuentes, Nora, Eugenia Gonzalez, Maria, O’Briain, Diarmuid, Carton, Edmund G., Sen, Ayan, Palacios, Amanda, Rainey, Deborah, Samoukoviv, Gordan, Campisi, Josie, Durham, Lucia, Neumann, Emily, Seefeldt, Cassandra, Falcucci, Octavio, Emmrich, Amanda, Guy, Jennifer, Johns, Carling, Potzner, Kelly, Zimmermann, Catherine, Espinal, Angelia, Buchtele, Nina, Schwameis, Michael, Korhnfehl, Andrea, Brock, Roman, Staudinger, Thomas, Stecher, Stephanie-Susanne, Barnikel, Michaela, Antón, Sófia, Pawlikowski, Alexandra, Zaaqoq, Akram, Anh Galloway, Lan, Merley, Caitlin, Nichol, Alistair, Csete, Marc, Quesada, Luisa, Saba, Isabela, Kasugai, Daisuke, Hiraiwa, Hiroaki, Tanaka, Taku, Marwali, Eva, Purnama, Yoel, Rahayu Dewayanti, Santi, Ardiyan, Arifa Juzar, Dafsah, Siagian, Debby, Chen, Yih-Sharng, Ogino, Mark, Ratsep, Indrek, Post, Andra-Maris, Sillaots, Piret, Krund, Anneli, Lehiste, Merili-Helen, Lepik, Tanel, Manetta, Frank, Mihelis, Effe, Claire Sarmiento, Iam, Narasimhan, Mangala, Varrone, Michael, Komats, Mamoru, Garcia-Diaz, Julia, Harmon, Catherine, Veena Satyapriya, S., Bhatt, Amar, Mokadam, Nahush A., Uribe, Alberto, Gonzalez, Alicia, Shi, Haixia, McKeown, Johnny, Pasek, Joshua, Fiorda, Juan, Echeverria, Marco, Moreno, Rita, Zakhary, Bishoy, Cavana, Marco, Cucino, Alberto, Foti, Giuseppe, Giani, Marco, Fumagalli, Benedetta, Chiumello, Davide, Castagna, Valentina, Dell’Amore, Andrea, Navalesi, Paolo, Shum, Hoi-Ping, Vuysteke, Alain, Usman, Asad, Acker, Andrew, Smood, Benjamin, Mergler, Blake, Sertic, Federico, Subramanian, Madhu, Sperry, Alexandra, Rizer, Nicolas, Burhan, Erlina, Rasmin, Menaldi, Akmal, Ernita, Sitompul, Faya, Lolong, Navy, Naivedh, Bhat, Erickson, Simon, Barrett, Peter, Dean, David, Daugherty, Julia, Loforte, Antonio, Khan, Irfan, Abraar Quraishi, Mohammed, DeSantis, Olivia, So, Dominic, Kandamby, Darshana, Mandei, Jose M., Natanael, Hans, YudhaLantang, Eka, Lantang, Anastasia, Oto Wijaya, Surya, Jung, Anna, Ng, George, Yiu Ng, Wing, Yeung Ng, Pauline, Fang, Shu, Tabah, Alexis, Ratcliffe, Megan, Duroux, Maree, Adachi, Shingo, Nakao, Shota, Blanco, Pablo, Prieto, Ana, Sánchez, Jesús, Nicholson, Meghan, Butt, Warwick, Serratore, Alyssa, Delzoppo, Carmel, Janin, Pierre, Yarad, Elizabeth, Totaro, Richard, Coles, Jennifer, Pujo, Bambang, Balk, Robert, Vissing, Andy, Kapania, Esha, Hays, James, Fox, Samuel, Yantosh, Garrett, Mishin, Pavel, Yuliarto, Saptadi, Hari Santoso, Kohar, Djajalaksana, Susanthy, Zainul Fatoni, Arie, Fukuda, Masahiro, Liu, Keibun, Pelosi, Paolo, Battaglini, Denise, Masa Jiménez, Juan Fernando, Bastos, Diego, Gaião, Sérgio, Rusmawatiningtyas, Desy, Cho, Young-Jae, Hwan Lee, Su, Kawasaki, Tatsuya, Munshi, Laveena, Sakiyalak, Pranya, Nitayavardhana, Prompak, Seitz, Tamara, Arora, Rakesh, Kent, David, Marino, Daniel, Parwar, Swapnil, Cheng, Andrew, Miller, Jennene, Fujitani, Shigeki, Shimizu, Naoki, Madhok, Jai, Owyang, Clark, Buscher, Hergen, Reynolds, Claire, Maasikas, Olavi, Beljantsev, Aleksan, Mihnovits, Vladislav, Akimoto, Takako, Aizawa, Mariko, Horibe, Kanako, Onodera, Ryota, Hodgson, Carol, Burrell, Aidan, Young, Meredith, George, Timothy, Shekar, Kiran, McGuinness, Niki, Irvine, Lacey, Flynn, Brigid, Endo, Tomoyuki, Sugiyama, Kazuhiro, Shimizu, Keiki, Fan, Eddy, Exconde, Kathleen, Ichiba, Shingo, Lussier, Leslie, Lotz, Gösta, Malfertheiner, Maximilian, Maier, Lars, Dreier, Esther, Permata Kusumastuti, Neurinda, McCloskey, Colin, Dabaliz, Al-Awwab, Elshazly, Tarek B, Smith, Josiah, Szuldrzynski, Konstanty S., Bielański, Piotr, Hakeem, Yusuff, Wille, Keith, Murthy, Srinivas, Parhar, Ken Kuljit S., Fiest, Kirsten M., Codan, Cassidy, Shahid, Anmol, Fayed, Mohamed, Evans, Timothy, Garcia, Rebekah, Gutierrez, Ashley, Shimizu, Hiroaki, Song, Tae, Rose, Rebecca, Bennett, Suzanne, Richardson, Denise, Peek, Giles, Arora, Lovkesh, Rappapport, Kristina, Rudolph, Kristina, Sibenaller, Zita, Stout, Lori, Walter, Alicia, Herr, Daniel, Vedadi, Nazli, Bartlett, Robert, Pesenti, Antonio, Thompson, Shaun, Hoffman, Julie, Ying, Xiaonan, Kennedy, Ryan, Elhadi, Muhammed, Griffee, Matthew, Ciullo, Anna, Kida, Yuri, Ferrer Roca, Ricard, Riera, JordI, Contreras, Sofia, Alegre, Cynthia, Kay, Christy, Fischer, Irene, Renner, Elizabeth, Taniguci, Hayato, Fraser, John, Li Bassi, Gianluigi, Suen, Jacky, Barnett, Adrian, White, Nicole, Gibbons, Kristen, Forsyth, Simon, Corley, Amanda, Pearse, India, Hinton, Samuel, Abbate, Gabriella, Hassan, Halah, Heinsar, Silver, Karnik, Varun A, Ki, Katrina, O’Neill, Hollier F., Obonyo, Nchafatso, Pretti Pimenta, Leticia, Reid, Janice D., Sato, Kei, Shekar, Kiran, Vuorinen, Aapeli, Wildi, Karin S., Wilson, Emily S., Yerkovich, Stephanie, Lee, James, Plotkin, Daniel, Wanjiru Citarella, Barbara, Merson, Laura, Hartley, Emma, Lubis, Bastian, Ikeyama, Takanari, Bhaskar, Balu, Jung, Jae-Seung, McGuinness, Shay, Eastwood, Glenn, Rossi Marta, Sandra, Guarracino, Fabio, Gerle, Stacy, Coxon, Emily, Claro, Bruno, Loverde, Daniel, Patil, Namrata, Parrini, Vieri, McBride, Angela, Negaard, Kathryn, Ratsch, Angela, Abdelaziz, Ahmad, David Uribe, Juan, Peris, Adriano, Sanders, Mark, Emerson, Dominic, Kamal, Muhammad, Povoa, Pedro, Francis, Roland, Cherif, Ali, Joseph, Sunimol, Di Nardo, Matteo, Heard, Micheal, Kyle, Kimberly, Blackwell, Ray A, Piagnerelli, Michael, Biston, Patrick, Won Jeong, Hye, Smith, Reanna, Prawira, Yogi, Montrucchio, Giorgia, Huerta Garcia, Arturo, Salterain, Nahikari, Meyns, Bart, Moreno, Marsha, Walia, Rajat, Mehta, Amit, Schweda, Annette, Supriatna, Moh, Kirakli, Cenk, Williams, Melissa, Hoon Kim, Kyung, Assad, Alexandra, Giraldo, Estefania, Karolak, Wojtek, Balik, Martin, Pocock, Elizabeth, Gajkowski, Evan, Masafumi, Kanamoto, Barrett, Nicholas, Takeyama, Yoshihiro, Park, Sunghoon, Amin, Faizan, Meilyana Andriyani, Fina, Sudakevych, Serhii, Ratsch, Angela, Vera, Magdalena, Cornejo, Rodrigo, Schwarz, Patrícia, Carolina Mardini, Ana, de Paula, Thais, Serpa Neto, Ary, Villoldo, Andrea, Siciliano Colafranceschi, Alexandre, Ubeda Iglesias, Alejandro, Granjean, Juan, Melro, Lívia Maria Garcia, Fioravante Romualdo, Giovana, Gaia, Diego, Souza, Helmgton, Galas, Filomena, Máñez Mendiluce, Rafael, Sosa, Alejandra, Martinez, Ignacio, Kurosawa, Hiroshi, Salgado, Juan, Hugi-Mayr, Beate, Charbonneau, Eric, Salvatore Barzilai, Vitor, Monteiro, Veronica, Ribeiro de Souza, Rodrigo, Harper, Michael, Suzuki, Hiroyuki, Adams, Celina, Brieva, Jorge, Nyale, George, Saleem Eltatar, Faisal, Fatani, Jihan, Baeissa, Husam, Masri, Ayman AL, Rabie, Ahmed, Yee Hui, Mok, Yamane, Masahiro, Jung, Hanna, Mojisola Margaret, Ayorinde, Nacpil, Newell, Ruck, Katja, Bakken, Rhonda, Jara, Claire, Felton, Tim, Berra, Lorenzo, Shah, Bobby, Chakraborty, Arpan, Cardona, Monika, Capatos, Gerry, Akkanti, Bindu, Orija, Abiodun, Jain, Harsh, Ito, Asami, Housni, Brahim, Low, Sennen, Iihara, Koji, Chavez, Joselito, Ramanathan, Kollengode, Zabert, Gustavo, Naidoo, Krubin, Seppelt, Ian, VanDyk, Marlice, MacDonald, Sarah, Ichiba, Shingo, McGregor, Randy, Siebenaler, Teka, Flynn, Hannah, Lofton, Kristi, Aokage, Toshiyuki, Shigemitsu, Kazuaki, Moscatelli, Andrea, Fiorentino, Giuseppe, Baumgaertel, Matthias, Eddy, Serge, Assy, Jana, Hutahaean, Amelya, Roush, Holly, Sichting, Kay A, Alessandri, Francesco, Burns, Debra, Rabie, Ahmed, Salt, Gavin, Garabedian, Carl P., Millar, Jonathan, Sim, Malcolm, Mattke, Adrian, McAuley, Danny, Tadili, Jawad, Frenzel, Tim, Bar-Lavie, Yaron, Blandino Ortiz, Aaron, Stone, Jackie, Tabah, Alexis, Attokaran, Antony, Farquharson, Michael, Patel, Brij, Gunning, Derek, Baillie, Kenneth, Watson, Pia, Tamai, Kenji, Ketut Sajinadiyasa, Gede, Kanyawati, Dyah, Salgado, Marcello, Sassine, Assad, Yudo, Bhirowo, McCaul, Scott, Lee, Bongjin, Min Lee, Sang, Afek, Arnon, Iwashita, Yoshiaki, Pujo Semedi, Bambang, Permata Kusumastuti, Neurinda, Metiva, Jack, Van Belle, Nicole, Martin-Loeches, Ignacio, Ivatt, Lenny, Yew Woon, Chia, Mi Kang, Hyun, Smith, Timothy, James, Erskine, Al-Rawas, Nawar, Iwasaki, Yudai, Chan King-Chung, Kenny, Gudzenko, Vadim, Hugi-Mayr, Beate, Taccone, Fabio, Perdhana, Fajar, Lamarche, Yoan, Miguel Ribeiro, Joao, Bradic, Nikola, Van den Bossche, Klaartje, Lansink, Oude, Singh, Gurmeet, Debeuckelaere, Gerdy, Stelfox, Henry T., Yi, Cassia, Elia, Jennifer, Tribble, Thomas, Shankar, Shyam, Padmanabhan, Raj, Hallinan, Bill, Paoletti, Luca, Leyva, Yolanda, Fykuda, Tatuma, Badulak, Jenelle, Koch, Jillian, Hackman, Amy, Janowaik, Lisa, Hernandez, Deb, Osofsky, Jennifer, Donadello, Katia, Lawang, Aizah, Fine, Josh, Davidson, Benjamin, and Vazquez, Andres Oswaldo Razo

Published
2023
Full Text
View/download PDF

28. Hosting Art Exhibits to Enhance Student Engagement: A Case Study at a Commuter College

Author

Rose, Rebecca, Nesbitt, Teresa, and Galloup, Allison

Abstract

A commuter campus library hosted an art exhibit in November 2019 to increase engagement levels of local high school and university students and to involve them in scholarly activities. The exhibit displayed student, faculty, and staff submissions on campus. The library space on campus features comfortable seating and desktop computers, with a collection robust with virtual holdings, but scant print volumes. Without physical print books, the library lacks the overt visual cues that can prompt students to seek out traditional library services. To increase student interactions, the librarians use outreach efforts to promote library services. Data collected via surveys from the event participants attempted to measure the impact that the event had on awareness of library services by participants.

Published
2020
Full Text
View/download PDF

30. A comparison of newer classifications of bronchopulmonary dysplasia: findings from the Children’s Hospitals Neonatal Consortium Severe BPD Group

Author

Vyas-Read, Shilpa, Logan, J. Wells, Cuna, Alain C., Machry, Joana, Leeman, Kristin T., Rose, Rebecca S., Mikhael, Michel, Wymore, Erica, Ibrahim, John W., DiGeronimo, Robert J., Yallapragada, Sushmita, Haberman, Beth E., Padula, Michael A., Porta, Nicolas F., Murthy, Karna, Nelin, Leif D., Coghill, Carl H., Zaniletti, Isabella, Savani, Rashmin C., Truog, William, Engle, William A., and Lagatta, Joanne M.

Published
2022
Full Text
View/download PDF

31. Brain-specific HIV Nef identified in multiple patients with neurological disease

Author

Lamers, Susanna L, Fogel, Gary B, Liu, Enoch S, Barbier, Andrew E, Rodriguez, Christopher W, Singer, Elyse J, Nolan, David J, Rose, Rebecca, and McGrath, Michael S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Neurosciences, Infectious Diseases, Biotechnology, HIV/AIDS, 2.2 Factors relating to the physical environment, Aetiology, Infection, Neurological, Good Health and Well Being, AIDS Dementia Complex, Amino Acid Sequence, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Autopsy, Binding Sites, Brain, Gene Expression, HIV-1, Host-Pathogen Interactions, Humans, Lymphoid Tissue, Macrophages, Models, Molecular, Neural Networks, Computer, Organ Specificity, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Sequence Alignment, Sequence Homology, Amino Acid, Signal Transduction, nef Gene Products, Human Immunodeficiency Virus, HIV, Neurological disease, Nef protein, Analytical classification tools, Clinical Sciences, Virology, Clinical sciences, Medical microbiology
Abstract

HIV-1 Nef is a flexible, multifunctional protein with several cellular targets that is required for pathogenicity of the virus. This protein maintains a high degree of genetic variation among intra- and inter-host isolates. HIV Nef is relevant to HIV-associated neurological diseases (HAND) in patients treated with combined antiretroviral therapy because of the protein's role in promoting survival and migration of infected brain macrophages. In this study, we analyzed 2020 HIV Nef sequences derived from 22 different tissues and 31 subjects using a novel computational approach. This approach combines statistical regression and evolved neural networks (ENNs) to classify brain sequences based on the physical and chemical characteristics of functional Nef domains. Based on training, testing, and validation data, the method successfully classified brain Nef sequences at 84.5% and provided informative features for further examination. These included physicochemical features associated with the Src-homology-3 binding domain, the Nef loop (including the AP-2 Binding region), and a cytokine-binding domain. Non-brain sequences from patients with HIV-associated neurological disease were frequently classified as brain, suggesting that the approach could indicate neurological risk using blood-derived virus or for the development of biomarkers for use in assay systems aimed at drug efficacy studies for the treatment of HIV-associated neurological diseases.

Published
2018

32. The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy

Author

Nolan, David J, Rose, Rebecca, Rodriguez, Patricia H, Salemi, Marco, Singer, Elyse J, Lamers, Susanna L, and McGrath, Michael S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Infectious Diseases, Infection, Good Health and Well Being, Adult, Aged, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Genes, gag, HIV Infections, HIV Seropositivity, HIV-1, Humans, Male, Middle Aged, Phylogeny, Polymerase Chain Reaction, Proviruses, RNA, Viral, Spleen, Viral Load, Viral Proteins, HIV evolution, viral reservoirs, phylogenetics, lymphatic system, Clinical Sciences, Virology, Clinical sciences
Abstract

Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.

Published
2018

33. Eradication of HIV from Tissue Reservoirs: Challenges for the Cure

Author

Rose, Rebecca, Nolan, David J, Maidji, Ekaterina, Stoddart, Cheryl A, Singer, Elyse J, Lamers, Susanna L, and McGrath, Michael S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Aetiology, 2.1 Biological and endogenous factors, Infection, Anti-HIV Agents, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Central Nervous System, HIV Infections, HIV-1, Humans, Lymph Nodes, Macrophages, RNA, Viral, Tissue Banks, Viral Load, Virus Latency, cure, cART, persistence, evolution, replication, compartment, Clinical Sciences, Virology, Clinical sciences
Abstract

The persistence of HIV infection, even after lengthy and successful combined antiretroviral therapy (cART), has precluded an effective cure. The anatomical locations and biological mechanisms through which the viral population is maintained remain unknown. Much research has focused nearly exclusively on circulating resting T cells as the predominant source of persistent HIV, a strategy with limited success in developing an effective cure strategy. In this study, we review research supporting the importance of anatomical tissues and other immune cells for HIV maintenance and expansion, including the central nervous system, lymph nodes, and macrophages. We present accumulated research that clearly demonstrates the limitations of using blood-derived cells as a proxy for tissue reservoirs and sanctuaries throughout the body. We cite recent studies that have successfully used deep-sequencing strategies to uncover the complexity of HIV infection and the ability of the virus to evolve despite undetectable plasma viral loads. Finally, we suggest new strategies and highlight the importance of tissue banks for future research.

Published
2018

34. A bioinformatic analysis of T-cell epitope diversity in SARS-CoV-2 variants: association with COVID-19 clinical severity in the United States population

Author

Kim, Grace J., primary, Elnaggar, Jacob H., additional, Varnado, Mallory, additional, Feehan, Amy K., additional, Tauzier, Darlene, additional, Rose, Rebecca, additional, Lamers, Susanna L., additional, Sevalia, Maya, additional, Nicholas, Najah, additional, Gravois, Elizabeth, additional, Fort, Daniel, additional, Crabtree, Judy S., additional, and Miele, Lucio, additional

Published
2024
Full Text
View/download PDF

36. Multi-model Assessment of Air Pollution-Related Premature Mortality in Europe and U.S.: Domestic Versus Foreign Contributions

Author

Im, Ulas, Brandt, Jørgen, Geels, Camilla, Hansen, Kaj Mantzius, Christensen, Jesper Heile, Andersen, Mikael Skou, Solazzo, Efisio, Kioutsioukis, Ioannis, Alyuz, Ummugulsum, Balzarini, Alessandra, Baro, Rocio, Bellasio, Roberto, Bianconi, Roberto, Bieser, Johannes, Colette, Augustin, Curci, Gabriele, Farrow, Aidan, Flemming, Johannes, Fraser, Andrea, Jimenez-Guerrero, Pedro, Kitwiroon, Nutthida, Liang, Ciao-Kai, Nopmongcol, Uarporn, Pirovano, Guido, Pozzoli, Luca, Prank, Marje, Rose, Rebecca, Sokhi, Ranjeet, Tuccella, Paolo, Unal, Alper, Vivanco, Marta Garcia, West, Jason, Yarwood, Greg, Hogrefe, Christian, Galmarini, Stefano, Mensink, Clemens, editor, Gong, Wanmin, editor, and Hakami, Amir, editor

Published
2020
Full Text
View/download PDF

39. Platforma 3

Author

Kuhar, Lea, primary, Petrevski, Dragan, primary, Zalar, Vita, primary, Cvar, Nina, primary, Grmek, Magdalena, primary, Jan, Matija, primary, Kusterle, Jernej, primary, Manzoni, Dino, primary, Rose, Rebecca, primary, and Tomšič, Neja, primary

Published
2022
Full Text
View/download PDF

40. Identifying Transmission Clusters with Cluster Picker and HIV-TRACE

Author

Rose, Rebecca, Lamers, Susanna L, Dollar, James J, Grabowski, Mary K, Hodcroft, Emma B, Ragonnet-Cronin, Manon, Wertheim, Joel O, Redd, Andrew D, German, Danielle, and Laeyendecker, Oliver

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Genetics, HIV/AIDS, Good Health and Well Being, Adolescent, Adult, Cluster Analysis, Disease Transmission, Infectious, Female, HIV, HIV Infections, Humans, Male, Middle Aged, Molecular Epidemiology, Sequence Analysis, DNA, Young Adult, viral clustering, Uganda, Virology, Clinical sciences
Abstract

We compared the behavior of two approaches (Cluster Picker and HIV-TRACE) at varying genetic distances to identify transmission clusters. We used three HIV gp41 sequence datasets originating from the Rakai Community Cohort Study: (1) next-generation sequence (NGS) data from nine linked couples; (2) NGS data from longitudinal sampling of 14 individuals; and (3) Sanger consensus sequences from a cross-sectional dataset (n = 1,022) containing 91 epidemiologically linked heterosexual couples. We calculated the optimal genetic distance threshold to separate linked versus unlinked NGS datasets using a receiver operating curve analysis. We evaluated the number, size, and composition of clusters detected by Cluster Picker and HIV-TRACE at six genetic distance thresholds (1%-5.3%) on all three datasets. We further tested the effect of using all NGS, versus only a single variant for each patient/time point, for datasets (1) and (2). The optimal gp41 genetic distance threshold to distinguish linked and unlinked couples and individuals was 5.3% and 4%, respectively. HIV-TRACE tended to detect larger and fewer clusters, whereas Cluster Picker detected more clusters containing only two sequences. For NGS datasets (1) and (2), HIV-TRACE and Cluster Picker detected all linked pairs at 3% and 4% genetic distances, respectively. However, at 5.3% genetic distance, 20% of couples in dataset (3) did not cluster using either program, and for >1/3 of couples cluster assignment were discordant. We suggest caution in choosing thresholds for clustering analyses in a generalized epidemic.

Published
2017

41. Single Genome Sequencing of Expressed and Proviral HIV-1 Envelope Glycoprotein 120 (gp120) and nef Genes.

Author

Nolan, David J, Lamers, Susanna L, Rose, Rebecca, Dollar, James J, Salemi, Marco, and McGrath, Michael S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, HIV/AIDS, Prevention, Immunization, Vaccine Related (AIDS), Genetics, Infectious Diseases, Human Genome, Clinical Research, Vaccine Related, Infection, Good Health and Well Being, HIV-1, Single genome sequencing, SGS, Gene amplification, Nested PCR, Biological sciences, Biomedical and clinical sciences
Abstract

The current study provides detailed protocols utilized to amplify the complete HIV-1 gp120 and nef genes from single copies of expressed or integrated HIV present in fresh-frozen autopsy tissues of patients who died while on combined antiretroviral therapy (cART) with no detectable plasma viral load (pVL) at death ( Lamers et al., 2016a and 2016b; Rose et al., 2016 ). This method optimizes protocols from previous publications ( Palmer et al., 2005 ; Norström et al., 2012 ; Lamers et al., 2015 ; 2016a and 2016b; Rife et al., 2016 ) to produce single distinct PCR products that can be directly sequenced and includes several cost-saving and time-efficient modifications.

Published
2017

42. The evolution of the private art museum in Mexico

Author

Rose, Rebecca

Subjects
708, NX Arts in general
Abstract

Over the last thirty years there has been a proliferation in the number and diversity of privately- funded exhibition spaces for contemporary art in Mexico. Driving this development is a new generation of art collectors and my research project is concerned with how collector-led models of patronage have influenced the recognition, impact and public display of contemporary art in Mexico. My thesis begins by exploring what constitutes an art collection, the significance of a museum, and what motivates a collector. I then present an overview of the historical relationship between state and private art collections in Mexico, followed by a critique of landmark events in the genesis of the Mexican art market. In the second part of my research project I identify a group of influential mid-twentieth century collectors who established their own exhibition spaces in order to share their collections with the public, followed by an analysis of their legacy through the activity of the current generation of collectors, whose efforts to promote contemporary art within Mexico and abroad have spawned a new climate of creative enterprise and collaboration. This thesis seeks to present a survey of the evolution of the private exhibition space in Mexico by examining independent cultural initiatives whose ambition is to change the way the public engages with contemporary art. In my findings I examine how collectors’ objectives manifest a vision for the museum visitor experience and the impact of these privately-funded institutions on Mexico’s cultural identity.

Published
2016

47. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

Author

Lamers, Susanna L, Rose, Rebecca, Maidji, Ekaterina, Agsalda-Garcia, Melissa, Nolan, David J, Fogel, Gary B, Salemi, Marco, Garcia, Debra L, Bracci, Paige, Yong, William, Commins, Deborah, Said, Jonathan, Khanlou, Negar, Hinkin, Charles H, Sueiras, Miguel Valdes, Mathisen, Glenn, Donovan, Suzanne, Shiramizu, Bruce, Stoddart, Cheryl A, McGrath, Michael S, and Singer, Elyse J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Neurosciences, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Infection, Anti-Retroviral Agents, Autopsy, DNA, Viral, HIV Infections, Humans, Longitudinal Studies, Real-Time Polymerase Chain Reaction, Viral Load, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

UnlabelledHIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis.ImportanceIt is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is, "Where is HIV hiding?" A well-studied HIV reservoir is "resting" T cells, which can be isolated from blood products and succumb to cART once activated. Less-studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since 50% of tissues were HIV infected. Additionally, we identified considerable pathology in participants' tissues, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. This study substantiates that tissue-associated HIV is present despite cART and can inform future studies into HIV persistence.

Published
2016

48. HIV Maintains an Evolving and Dispersed Population in Multiple Tissues during Suppressive Combined Antiretroviral Therapy in Individuals with Cancer

Author

Rose, Rebecca, Lamers, Susanna L, Nolan, David J, Maidji, Ekaterina, Faria, NR, Pybus, Oliver G, Dollar, James J, Maruniak, Samuel A, McAvoy, Andrew C, Salemi, Marco, Stoddart, Cheryl A, Singer, Elyse J, and McGrath, Michael S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Biotechnology, Infectious Diseases, Cancer, HIV/AIDS, Genetics, Aetiology, 2.2 Factors relating to the physical environment, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Autopsy, Cerebellum, DNA, Viral, Genetic Variation, HIV, HIV Infections, In Situ Hybridization, Lymph Nodes, Neoplasms, Phylogeny, RNA, Viral, Sequence Analysis, DNA, Sequence Homology, Sustained Virologic Response, Viral Load, env Gene Products, Human Immunodeficiency Virus, nef Gene Products, Human Immunodeficiency Virus, pol Gene Products, Human Immunodeficiency Virus, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Virology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

UnlabelledWhile combined antiretroviral therapy (cART) can result in undetectable plasma viral loads, it does not eradicate HIV infection. Furthermore, HIV-infected individuals while on cART remain at an increased risk of developing serious comorbidities, such as cancer, neurological disease, and atherosclerosis, suggesting that during cART, tissue-based HIV may contribute to such pathologies. We obtained DNA and RNA env, nef, and pol sequences using single-genome sequencing from postmortem tissues of three HIV(+) cART-treated (cART(+)) individuals with undetectable viral load and metastatic cancer at death and performed time-scaled Bayesian evolutionary analyses. We used a sensitive in situ hybridization technique to visualize HIV gag-pol mRNA transcripts in cerebellum and lymph node tissues from one patient. Tissue-associated virus evolved at similar rates in cART(+) and cART-naive (cART(-)) patients. Phylogenetic trees were characterized by two distinct features: (i) branching patterns consistent with constant viral evolution and dispersal among tissues and (ii) very recently derived clades containing both DNA and RNA sequences from multiple tissues. Rapid expansion of virus near death corresponded to wide-spread metastasis. HIV RNA(+) cells clustered in cerebellum tissue but were dispersed in lymph node tissue, mirroring the evolutionary patterns observed for that patient. Activated, infiltrating macrophages were associated with HIV RNA. Our data provide evidence that tissues serve as a sanctuary for wild-type HIV during cART and suggest the importance of macrophages as an alternative reservoir and mechanism of virus spread.ImportanceCombined antiretroviral therapy (cART) reduces plasma HIV to undetectable levels; however, removal of cART results in plasma HIV rebound, thus highlighting its inability to entirely rid the body of infection. Additionally, HIV-infected individuals on cART remain at high risk of serious diseases, which suggests a contribution from residual HIV. In this study, we isolated and sequenced HIV from postmortem tissues from three HIV(+) cART(+) individuals who died with metastatic cancer and had no detectable plasma viral load. Using high-resolution evolutionary analyses, we found that tissue-based HIV continues to replicate, evolve, and migrate among tissues during cART. Furthermore, cancer onset and metastasis coincided with increased HIV expansion, suggesting a linked mechanism. HIV-expressing cells were associated with tissue macrophages, a target of HIV infection. Our results suggest the importance of tissues, and macrophages in particular, as a target for novel anti-HIV therapies.

Published
2016

49. Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

Author

Raghwani, Jayna, Rose, Rebecca, Sheridan, Isabelle, Lemey, Philippe, Suchard, Marc A, Santantonio, Teresa, Farci, Patrizia, Klenerman, Paul, and Pybus, Oliver G

Subjects
Humans, Hepacivirus, HIV-1, Hepatitis C, Chronic, HIV Infections, Follow-Up Studies, Evolution, Molecular, Virus Replication, Female, Male, Evolution, Molecular, Hepatitis C, Chronic, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.

Published
2016

50. The meningeal lymphatic system: a route for HIV brain migration?

Author

Lamers, Susanna L, Rose, Rebecca, Ndhlovu, Lishomwa C, Nolan, David J, Salemi, Marco, Maidji, Ekaterina, Stoddart, Cheryl A, and McGrath, Michael S

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Neurosciences, Infectious Diseases, HIV/AIDS, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Infection, AIDS Dementia Complex, Blood-Brain Barrier, Brain, Cell Movement, Chemokines, Dendritic Cells, Endothelium, Vascular, HIV-1, Humans, Lymphatic System, Macrophages, Meninges, Monocytes, T-Lymphocytes, Virus Internalization, HIV brain infection, Lymphatic system, Neurological disease, Macrophage-targeted therapy, Clinical Sciences, Virology, Clinical sciences, Medical microbiology
Abstract

Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results