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Founder virus

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
HIV-1 infection often arises from a single transmitted/founder (TF) viral variant, amongst a large pool of viruses in the quasispecies in the transmitting partner. TF variants are typically non-dominant in blood and genital secretions, indicating unique traits. The plasmacytoid dendritic cell (pDC) is the primary IFN-α producing cell in response to viral infections, and is rapidly recruited to the female genital tract upon exposure to HIV-1. The impact of the pDC on transmission is unknown. We investigated whether evasion of pDC responses was a trait of TF viruses...
July 11, 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 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...
June 20, 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...
May 25, 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
Agnes-Laurence Chenine, Melanie Merbah, Lindsay Wieczorek, Sebastian Molnar, Brendan Mann, Jenica Lee, Anne-Marie OʼSullivan, Meera Bose, Eric Sanders-Buell, Gustavo H Kijak, Carolina Herrera, Robert McLinden, Robert J OʼConnell, Nelson L Michael, Merlin L Robb, Jerome H Kim, Victoria R Polonis, Sodsai Tovanabutra
BACKGROUND: HIV-1 CRF01_AE is dominant in Thailand where RV144 vaccine trial was conducted. To study immune correlates of protection in ongoing trials, CRF01_AE-derived reagents are essential. Here, we present a panel of 14 HIV-1 infectious molecular clones (IMCs) identified from different stages of infection and characterization of their neutralization sensitivity using 2 standard assays. METHODS: One full-length IMC was constructed using a transmitted-founder virus to express Renilla luciferase (LucR) reporter gene and full-length envelopes (envs) of exogenous HIV-1...
July 1, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
E S Orton, C M Brasier, L J Bilham, A Bansal, J F Webber, J K M Brown
The ash dieback fungus, Hymenoscyphus fraxineus , a destructive, alien pathogen of common ash ( Fraxinus excelsior ), has spread across Europe over the past 25 years and was first observed in the UK in 2012. To investigate the relationship of the pathogen's population structure to its mode of arrival, isolates were obtained from locations in England and Wales, either where established natural populations of ash had been infected by wind-dispersed ascospores or where the fungus had been introduced on imported planting stock...
February 2018: Plant Pathology
Hong-Miao Liu, Ning-Ning Ma, Chun Luo, Shu-Ying Yuan, Fu-Li Liu, Xin-Gang Yao, Chun-Qiong Zhou, Min Zou
OBJECTIVE: To investigate the effect of semen-derived enhancer of virus infection (SEVI) on the infection of transmitted/founder (TF) HIV-1 and its matched chronic control (CC) viruses and the antagonism of ADS-J1 on SEVI-mediated enhancement of TF and CC virus infection in vitro. METHODS: PAP248-286 self-assembling into SEVI amyloid fibrils was validated by ThT assay. We generated the virus stocks of TF and CC virus pair. TZM-bl cells were infected with the mixture of SEVI and TF or CC viruses for 72 h...
February 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Vani G S Narasimhulu, Anna K Bellamy-McIntyre, Annamarie E Laumaea, Chan-Sien Lay, David N Harrison, Hannah A D King, Heidi E Drummer, Pantelis Poumbourios
HIV-1 is spread by cell-free virions and by cell-cell viral transfer. We asked whether the structure and function of a broad neutralizing antibody (bNAb) epitope, the membrane-proximal ectodomain region (MPER) of the viral gp41 transmembrane glycoprotein, differ in cell-free and cell-cell-transmitted viruses and whether this difference could be related to Ab neutralization sensitivity. Whereas cell-free viruses bearing W666A and I675A substitutions in the MPER lacked infectivity, cell-associated mutant viruses were able to initiate robust spreading infection...
April 20, 2018: Journal of Biological Chemistry
Manickam Ashokkumar, Shambhu G Aralaguppe, Srikanth P Tripathy, Luke Elizabeth Hanna, Ujjwal Neogi
Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses...
May 1, 2018: Journal of Virology
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