Read by QxMD icon Read

Founder virus

Linling He, Sonu Kumar, Joel D Allen, Deli Huang, Xiaohe Lin, Colin J Mann, Karen L Saye-Francisco, Jeffrey Copps, Anita Sarkar, Gabrielle S Blizard, Gabriel Ozorowski, Devin Sok, Max Crispin, Andrew B Ward, David Nemazee, Dennis R Burton, Ian A Wilson, Jiang Zhu
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For 10 strains across five clades, we demonstrate that the gp41 ectodomain (gp41ECTO ) is the main source of envelope metastability by replacing wild-type gp41ECTO with BG505 gp41ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41ECTO -swapped trimers can be produced in CHO cells with high yield and high purity. The crystal structure of a gp41ECTO -swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex...
November 2018: Science Advances
Yangtao Ji, Xiaoxu Han, Wen Tian, Yang Gao, Su Jin, Linqi Zhang, Hong Shang
To date, inducing the production of broadly neutralizing antibodies (bnAbs) against HIV-1 in humans has been unsuccessful. Several studies have explored the coevolution of HIV-1 and neutralizing antibodies (nAbs), but little is known about what affects the lack of bnAbs after long-term infection. A better understanding of the coevolution of the virus and nAbs in cases involving no bnAb production will help in the design of an effective HIV-1 vaccine. An individual with acute CRF01_AE HIV-1 infection who lacked bnAbs at just over 2 years post-infection (p...
November 29, 2018: Vaccine
Doreen Muth, Victor Max Corman, Hanna Roth, Tabea Binger, Ronald Dijkman, Lina Theresa Gottula, Florian Gloza-Rausch, Andrea Balboni, Mara Battilani, Danijela Rihtarič, Ivan Toplak, Ramón Seage Ameneiros, Alexander Pfeifer, Volker Thiel, Jan Felix Drexler, Marcel Alexander Müller, Christian Drosten
A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (-29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor...
October 11, 2018: Scientific Reports
Audra A Hargett, Qing Wei, Barbora Knoppova, Stacy Hall, Zhi-Qiang Huang, Amol Prakash, Todd J Green, Zina Moldoveanu, Milan Raska, Jan Novak, Matthew B Renfrow
The HIV-1 envelope (Env) glycans shield the surface of Env from the immune system and form integral interactions important for a functional Env. To understand how individual N-glycosylation sites (NGS) coordinate to form a dynamic shield and evade the immune system through mutations, we tracked 20 NGS in Env from HIV transmitted/founder (T/F) and immune-escape variants and their mutants involving the N262 glycan. NGS were profiled in a site-specific manner using a high-resolution mass spectrometry (MS)-based workflow...
October 10, 2018: Journal of Virology
Yaxelis Mendoza, Claudia García-Morales, Gonzalo Bello, Daniela Garrido-Rodríguez, Daniela Tapia-Trejo, Juan Miguel Pascale, Amalia Carolina Girón-Callejas, Ricardo Mendizábal-Burastero, Ingrid Yessenia Escobar-Urias, Blanca Leticia García-González, Jessenia Sabrina Navas-Castillo, María Cristina Quintana-Galindo, Rodolfo Pinzón-Meza, Carlos Rodolfo Mejía-Villatoro, Santiago Avila-Ríos, Gustavo Reyes-Terán
Different explanations exist on how HIV-1 subtype B spread in Central America, but the role of Guatemala, the Central American country with the highest number of people living with the virus, in this scenario is unknown. We investigated the evolutionary history and spatiotemporal dynamics of HIV-1 subtype B in Guatemala. A total of 1,047 HIV-1 subtype B pol sequences, from newly diagnosed ART-naïve, HIV-infected Guatemalan subjects enrolled between 2011 and 2013 were combined with published subtype B sequences from other Central American countries (n = 2,101) and with reference sequences representative of the BPANDEMIC and BCAR lineages from the United States (n = 465), France (n = 344) and the Caribbean (n = 238)...
2018: PloS One
Jonathon E Himes, Ria Goswami, Riley J Mangan, Amit Kumar, Thomas L Jeffries, Joshua A Eudailey, Holly Heimsath, Quang N Nguyen, Justin Pollara, Celia LaBranche, Meng Chen, Nathan A Vandergrift, James W Peacock, Faith Schiro, Cecily Midkiff, Guido Ferrari, David C Montefiori, Xavier Alvarez Hernandez, Pyone Pyone Aye, Sallie R Permar
Breast milk HIV-1 transmission is currently the predominant contributor to pediatric HIV infections. Yet, only ~10% of breastfeeding infants born to untreated HIV-infected mothers become infected. This study assessed the protective capacity of natural HIV envelope-specific antibodies isolated from the milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. To mimic placental and milk maternal antibody transfer, infant RMs were i.v. infused and orally treated at the time of challenge with a single weakly neutralizing milk monoclonal antibody (mAb), a tri-mAb cocktail with weakly neutralizing and ADCC functionalities, or an anti-influenza control mAb...
August 16, 2018: Mucosal Immunology
Jingyou Yu, Shan-Lu Liu
Interferon inducible transmembrane proteins (IFITMs) are one of several IFN-stimulated genes (ISGs) that restrict entry of enveloped viruses, including flaviviruses, filoviruses and retroviruses. It has been recently reported that in U87 glioblastoma cells IFITM proteins inhibit HIV-1 entry in a co-receptor-dependent manner, that is, IFITM1 is more inhibitory on CCR5 tropic HIV-1 whereas IFITM2/3 confers a greater suppression of CXCR4 counterparts. However, how entry of HIV-1 with distinct co-receptor usage is modulated by different IFITM orthologs in physiologically relevant CD4⁺ T cells and monocytes/macrophages has not been investigated in detail...
August 7, 2018: Viruses
César Trifone, Jimena Salido, María Julia Ruiz, Lin Leng, María Florencia Quiroga, Horacio Salomón, Richard Bucala, Yanina Ghiglione, Gabriela Turk
Understanding the mechanisms of human immunodeficiency virus type I (HIV-1) pathogenesis would facilitate the identification of new therapeutic targets to control the infection in face of current antiretroviral therapy limitations. CD74 membrane expression is upregulated in HIV-1-infected cells and the magnitude of its modulation correlates with immune hyperactivation in HIV-infected individuals. In addition, plasma level of the CD74 activating ligand macrophage migration inhibitory factor (MIF) is increased in infected subjects...
2018: Frontiers in Immunology
Jordan Ari Schwartz, Hongliang Zhang, Zachary Ende, Martin J Deymier, Terry Lee, Joel Singer, Tony Mazzulli, Eric Hunter, Mario A Ostrowski
Human immunodeficiency virus type 1 (HIV-1) infection often arises from a single transmitted/founder (TF) viral variant among a large pool of viruses in the quasispecies in the transmitting partner. TF variants are typically nondominant in blood and genital secretions, indicating that they have unique traits. The plasmacytoid dendritic cell (pDC) is the primary alpha interferon (IFN-α)-producing cell in response to viral infections and is rapidly recruited to the female genital tract upon exposure to HIV-1...
October 1, 2018: Journal of Virology
Vineet Joag, Aida Sivro, Nonhlanhla Yende-Zuma, Hajra Imam, Natasha Samsunder, Quarraisha Abdool Karim, Salim Abdool Karim, Lyle McKinnon, Rupert Kaul
BACKGROUND: A blood-based assay that could quantify HIV susceptibility would be very valuable for HIV prevention research. Previously, we developed and validated an ex vivo, flow-based, HIV entry assay to assess genital HIV susceptibility in endocervical CD4+ T cells. METHODS: Here we assessed whether this tool could be used to predict HIV risk using blood-derived CD4+ T cells in a rigorously-blinded, nested case-control study using blood samples collected from high-risk, HIV-uninfected South African women enrolled in the CAPRISA 004 clinical trial...
2018: PloS One
Egidio Brocca-Cofano, Cuiling Xu, Katherine S Wetzel, Mackenzie L Cottrell, Benjamin B Policicchio, Kevin D Raehtz, Dongzhu Ma, Tammy Dunsmore, George S Haret-Richter, Karam Musaitif, Brandon F Keele, Angela D Kashuba, Ronald G Collman, Ivona Pandrea, Cristian Apetrei
Current approaches do not eliminate all human immunodeficiency virus type 1 (HIV-1) maternal-to-infant transmissions (MTIT); new prevention paradigms might help avert new infections. We administered maraviroc (MVC) to rhesus macaques (RMs) to block CCR5-mediated entry, followed by repeated oral exposure of a CCR5-dependent clone of simian immunodeficiency virus (SIV) mac251 (SIVmac766). MVC significantly blocked the CCR5 coreceptor in peripheral blood mononuclear cells and tissue cells. All control animals and 60% of MVC-treated infant RMs became infected by the 6th challenge, with no significant difference between the number of exposures ( P = 0...
September 1, 2018: Journal of Virology
Dan Xiang, Zhiqing Pu, Tingting Luo, Fucheng Guo, Xiaobing Li, Xuejuan Shen, David M Irwin, Robert W Murphy, Ming Liao, Yongyi Shen
Since its emergence in March 2013, novel avian influenza A H7N9 virus has triggered five epidemics of human infections in China. This raises concerns about the pandemic threat of this quickly evolving H7N9 subtype for humans. In this study, we evaluated all available genomes for H7N9 and H9N2 influenza A viruses. Our assessment discovered that H7N9 of the 1st wave had the lowest nucleotide diversity, which then experienced substantial and rapid population expansion from a small founder population. From the 2nd wave, their nucleotide diversity increased quickly, indicating that H7N9 viruses had acquired larger populations and mutations after their initial emergence in 2013...
September 2018: Journal of Infection
Thorsten Krause, Stefanie Grote-Wessels, Felix Balzer, Peter Boknik, Ulrich Gergs, Uwe Kirchhefer, Igor B Buchwalow, Frank U Müller, Wilhelm Schmitz, Joachim Neumann
About half of the cardiac serine/threonine phosphatase activity is due to the activity of protein phosphatase type 1 (PP1). The activity of PP1 can be inhibited by an endogenous protein for which the expression inhibitor-2 (I-2) has been coined. We have previously described a transgenic mouse overexpressing a truncated form of I-2. Here, we have described and initially characterized several founders that overexpress the non-truncated (i.e., full length) I-2 in the mouse heart (TG) and compared them with non-transgenic littermates (WT)...
August 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Shakti Singh, Eric G Ramírez-Salazar, Rami Doueiri, Antonio Valentin, Margherita Rosati, Xintao Hu, Brandon F Keele, Xiaoying Shen, Georgia D Tomaras, Guido Ferrari, Celia LaBranche, David C Montefiori, Jishnu Das, Galit Alter, Hung V Trinh, Christopher Hamlin, Mangala Rao, Frances Dayton, Jenifer Bear, Bhabadeb Chowdhury, Candido Alicea, Jeffrey D Lifson, Kate E Broderick, Niranjan Y Sardesai, Sandra J Sivananthan, Christopher B Fox, Steven G Reed, David J Venzon, Vanessa M Hirsch, George N Pavlakis, Barbara K Felber
We developed a method of simultaneous vaccination with DNA and protein resulting in robust and durable cellular and humoral immune responses with efficient dissemination to mucosal sites and protection against simian immunodeficiency virus (SIV) infection. To further optimize the DNA-protein coimmunization regimen, we tested a SIVmac251 -based vaccine formulated with either of two Toll-like receptor 4 (TLR4) ligand-based liposomal adjuvant formulations (TLR4 plus TLR7 [TLR4+7] or TLR4 plus QS21 [TLR4+QS21]) in macaques...
August 1, 2018: Journal of Virology
Manxue Jia, Hong Lu, Xiang-Peng Kong, Cecilia Cheng-Mayer, Xueling Wu
Simian-human immunodeficiency virus (SHIV) infection provides a relevant animal model to study HIV-1 neutralization breadth. With previously identified SHIVSF162P3N infected rhesus macaques that did or did not develop neutralization breadth, we characterized the transmitted/founder viruses and initial autologous/homologous neutralizing antibodies in these animals. The plasma viral load and blood CD4 count did not distinguish macaques with and without breadth, and only one tested homologous envelope clone revealed a trend for macaques with breadth to favor an early homologous response...
May 16, 2018: Viruses
Debashis Dutta, Samuel Johnson, Alisha Dalal, Martin J Deymier, Eric Hunter, Siddappa N Byrareddy
Traditional restriction endonuclease-based cloning has been routinely used to generate replication-competent simian-human immunodeficiency viruses (SHIV) and simian tropic HIV (stHIV). This approach requires the existence of suitable restriction sites or the introduction of nucleotide changes to create them. Here, using an In-Fusion cloning technique that involves homologous recombination, we generated SHIVs and stHIVs based on epidemiologically linked clade C transmitted/founder HIV molecular clones from Zambia...
2018: PloS One
Amit Kumar, Claire E P Smith, Elena E Giorgi, Joshua Eudailey, David R Martinez, Karina Yusim, Ayooluwa O Douglas, Lisa Stamper, Erin McGuire, Celia C LaBranche, David C Montefiori, Genevieve G Fouda, Feng Gao, Sallie R Permar
Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U...
April 2018: PLoS Pathogens
Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wan, Jianqing Xu
Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission. We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 104 TCID50 ) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey...
2018: Frontiers in Microbiology
Alexander L Greninger, Giselle M Knudsen, Pavitra Roychoudhury, Derek J Hanson, Ruth Hall Sedlak, Hong Xie, Jon Guan, Thuy Nguyen, Vikas Peddu, Michael Boeckh, Meei-Li Huang, Linda Cook, Daniel P Depledge, Danielle M Zerr, David M Koelle, Soren Gantt, Tetsushi Yoshikawa, Mary Caserta, Joshua A Hill, Keith R Jerome
BACKGROUND: Human herpesvirus-6A and -6B (HHV-6) are betaherpesviruses that reach > 90% seroprevalence in the adult population. Unique among human herpesviruses, HHV-6 can integrate into the subtelomeric regions of human chromosomes; when this occurs in germ line cells it causes a condition called inherited chromosomally integrated HHV-6 (iciHHV-6). Only two complete genomes are available for replicating HHV-6B, leading to numerous conflicting annotations and little known about the global genomic diversity of this ubiquitous virus...
March 20, 2018: BMC Genomics
Adan Rios
There is consensus that only a preventive vaccine can contain the HIV/AIDS pandemic. After 30 years still there is no preventive HIV vaccine. This article examines fundamental challenges to the development of a preventive HIV vaccine. They include the initially erroneous but powerful perception of the natural history of HIV disease, as an acute rather than a chronic illness even in the absence of therapy, the lack of appreciation of the quasispecies biology of HIV and the abandonment of principles of immunology theory caused by the allure of technological prowess...
April 2018: Current Opinion in Virology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"