Phenotypic properties of transmitted founder HIV-1
Nicholas F. Parrish,Feng Gao,Hui Li,Elena E. Giorgi,Hannah J. Barbian,Erica H. Parrish,Lara Zajic,Shilpa S. Iyer,Julie M. Decker,Amit Kumar,Bhavna Hora,Anna Berg,Fangping Cai,Jennifer Hopper,Thomas N. Denny,Haitao Ding,Christina Ochsenbauer,John C. Kappes,Rachel P. Galimidi,Anthony P. West,Pamela J. Bjorkman,Craig B. Wilen,Robert W. Doms,Robert W. Doms,Meagan O’Brien,Nina Bhardwaj,Persephone Borrow,Barton F. Haynes,Mark Muldoon,James Theiler,Bette T. Korber,George M. Shaw,Beatrice H. Hahn +32 more
TLDR
TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance, which should be considered in the development and testing of AIDS vaccines.Abstract:
Defining the virus–host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most of these studies were limited to examining envelope (Env) function in the context of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated to higher titers than CC viruses. This difference was significant for subtype B (P = 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic differences of the respective patient cohorts. Together, these data indicate that TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance. These viral properties, which likely act in concert, should be considered in the development and testing of AIDS vaccines.read more
Citations
More filters
Journal Article
[Expression of fusion proteins in beta(2)GP I gene-transfected HEp-2 cells and its clinical application].
Liangjing Lu,Shunle Chen,Yue-ying Gu,Nan Shen,Chunde Bao,Yuan Wang,Chengde Yang,Ping Ye,Chong-zhao Yu +8 more
TL;DR: As a new kind of substrate of IIF, beta( 2)GP I transfectant can be used to detect anti-beta(2)GP-I antibodies and keep the immunofluorescent property of HEp-2 cells in IFANA test and can be use as substrate for routine IFANA detection.
Journal ArticleDOI
HIV infection: epidemiology, pathogenesis, treatment, and prevention
TL;DR: The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition and breakthroughs in the prevention of HIV important to public health include male medical circumcision.
Journal ArticleDOI
Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression
Netanya G. Sandler,Netanya G. Sandler,Steven E. Bosinger,Jacob D. Estes,Richard T R Zhu,Gregory K. Tharp,Eli Boritz,Doron Levin,Sathi Wijeyesinghe,Krystelle Nganou Makamdop,Gregory Q. Del Prete,Brenna J. Hill,J. Katherina Timmer,Emma Reiss,Ganit Yarden,Samuel Darko,Eduardo J. Contijoch,John Paul Todd,Guido Silvestri,Martha Nason,Robert B. Norgren,Brandon F. Keele,Srinivas S. Rao,Jerome A. Langer,Jeffrey D. Lifson,Gideon Schreiber,Daniel C. Douek +26 more
TL;DR: The timing ofIFN-induced innate responses in acute SIV infection profoundly affects overall disease course and outweighs the detrimental consequences of increased immune activation, yet the clinical consequences of manipulation of IFN signalling are difficult to predict in vivo and therapeutic interventions in human studies should be approached with caution.
Journal ArticleDOI
HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption
Johannes F. Scheid,Johannes F. Scheid,Joshua A. Horwitz,Yotam Bar-On,Edward F. Kreider,Ching-Lan Lu,Julio C. C. Lorenzi,Anna Feldmann,Malte Braunschweig,Lilian Nogueira,Thiago Y. Oliveira,Irina Shimeliovich,Roshni Patel,Leah A. Burke,Yehuda Z. Cohen,Sonya Hadrigan,Allison Settler,Maggi Witmer-Pack,Anthony P. West,Boris Juelg,Tibor Keler,Thomas Hawthorne,Barry S. Zingman,Roy M. Gulick,Nico Pfeifer,Gerald H. Learn,Michael S. Seaman,Pamela J. Bjorkman,Florian Klein,Florian Klein,Florian Klein,Sarah J. Schlesinger,Bruce D. Walker,Bruce D. Walker,Beatrice H. Hahn,Michel C. Nussenzweig,Marina Caskey +36 more
TL;DR: It is concluded that administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during ATI in humans, suggesting failure to escape over a period of 9-19 weeks.
Journal ArticleDOI
Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption
Katharine J. Bar,Michael C. Sneller,Linda Harrison,J. Shawn Justement,Edgar T. Overton,Mary E. Petrone,D. Brenda Salantes,Catherine Seamon,Benjamin Scheinfeld,Richard Kwan,Gerald H. Learn,Michael A. Proschan,Edward F. Kreider,Jana Blazkova,Mark Bardsley,Eric W. Refsland,Michael Messer,Katherine E Clarridge,Nancy B Tustin,Patrick J Madden,KaSaundra Oden,Sijy O'Dell,Bernadette Jarocki,Andrea Shiakolas,Randall Tressler,Nicole A. Doria-Rose,Robert T. Bailer,Julie E. Ledgerwood,Edmund V. Capparelli,Rebecca M. Lynch,Barney S. Graham,Susan Moir,Richard A. Koup,John R. Mascola,James A. Hoxie,Anthony S. Fauci,Pablo Tebas,Tae-Wook Chun +37 more
TL;DR: Analyses of virus populations before ART as well as before and after ART interruption showed that VRC01 exerted pressure on rebounding virus, resulting in restriction of recrudescent viruses and selection for preexisting and emerging antibody neutralization-resistant virus.
References
More filters
Journal ArticleDOI
Homozygous Defect in HIV-1 Coreceptor Accounts for Resistance of Some Multiply-Exposed Individuals to HIV-1 Infection
Rong Liu,William A. Paxton,Sunny Choe,Daniel Ceradini,Scott R. Martin,Richard Horuk,Marcy E. MacDonald,Heidi Stuhlmann,Richard A. Koup,Nathaniel R. Landau +9 more
TL;DR: A CKR-5 allele present in the human population appears to protect homozygous individuals from sexual transmission of HIV-1 and is suggested to provide a means of preventing or slowing disease progression.
Journal ArticleDOI
DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells
Teunis B.H. Geijtenbeek,Douglas S. Kwon,Ruurd Torensma,S.J. van Vliet,G.C.F. van Duijnhoven,J. Middel,I.L.M.H.A. Cornelissen,H.S.L.M. Nottet,Vineet N. KewalRamani,Dan R. Littman,Carl G. Figdor,Y. van Kooyk +11 more
TL;DR: It is proposed that DC-SIGN efficiently captures HIV-1 in the periphery and facilitates its transport to secondary lymphoid organs rich in T cells, to enhance infection in trans of these target cells.
Journal ArticleDOI
Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein
TL;DR: A unique cellular gene, CEM15, is described, whose transient or stable expression in cells that do not normally express Cem15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif.
Journal ArticleDOI
The nature of the principal type 1 interferon-producing cells in human blood.
Frederick P. Siegal,Norimitsu Kadowaki,Michael Shodell,Patricia Fitzgerald-Bocarsly,Kokila Shah,Stephen Ho,Svetlana Antonenko,Yong-Jun Liu +7 more
TL;DR: Purified IPCs are here shown to be the CD4(+)CD11c- type 2 dendritic cell precursors (pDC2s), which produce 200 to 1000 times more IFN than other blood cells after microbial challenge and are thus an effector cell type of the immune system, critical for antiviral and antitumor immune responses.
Journal ArticleDOI
A diverse range of gene products are effectors of the type I interferon antiviral response
John W. Schoggins,Sam J. Wilson,Maryline Panis,Mary Murphy,Christopher T. Jones,Paul D. Bieniasz,Charles M. Rice +6 more
TL;DR: It is shown that different viruses are targeted by unique sets of ISGs, and that each viral species is susceptible to multiple antiviral genes, which together encompass a range of inhibitory activities.
Related Papers (5)
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
Brandon F. Keele,Elena E. Giorgi,Elena E. Giorgi,Jesus F. Salazar-Gonzalez,Julie M. Decker,Kimmy T. Pham,Maria G. Salazar,Chuanxi Sun,Truman Grayson,Shuyi Wang,Hui Li,Xiping Wei,Chunlai Jiang,Jennifer L. Kirchherr,Feng Gao,Jeffery A. Anderson,Li Hua Ping,Ronald Swanstrom,Georgia D. Tomaras,William A. Blattner,Paul A. Goepfert,J. Michael Kilby,Michael S. Saag,Eric Delwart,Michael P. Busch,Myron S. Cohen,David C. Montefiori,Barton F. Haynes,Brian Gaschen,Gayathri Athreya,Ha Y. Lee,Natasha T. Wood,Cathal Seoighe,Alan S. Perelson,Tanmoy Bhattacharya,Tanmoy Bhattacharya,Bette T. Korber,Bette T. Korber,Beatrice H. Hahn,George M. Shaw +39 more
Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection.
Jesus F. Salazar-Gonzalez,Maria G. Salazar,Brandon F. Keele,Gerald H. Learn,Elena E. Giorgi,Elena E. Giorgi,Hui Li,Julie M. Decker,Shuyi Wang,Joshua Baalwa,Matthias H. Kraus,Nicholas F. Parrish,Katharina S. Shaw,M. Brad Guffey,Katharine J. Bar,Katie L. Davis,Christina Ochsenbauer-Jambor,John C. Kappes,Michael S. Saag,Myron S. Cohen,Joseph Mulenga,Cynthia A. Derdeyn,Susan Allen,Eric Hunter,Martin Markowitz,Martin Markowitz,Peter T. Hraber,Alan S. Perelson,Tanmoy Bhattacharya,Tanmoy Bhattacharya,Barton F. Haynes,Bette T. Korber,Bette T. Korber,Beatrice H. Hahn,George M. Shaw +34 more
Deciphering Human Immunodeficiency Virus Type 1 Transmission and Early Envelope Diversification by Single-Genome Amplification and Sequencing
Jesus F. Salazar-Gonzalez,Elizabeth Bailes,Kimmy T. Pham,Maria G. Salazar,M. Brad Guffey,Brandon F. Keele,Cynthia A. Derdeyn,Paul Farmer,Eric Hunter,Susan Allen,Olivier Manigart,Joseph Mulenga,Jeffrey A. Anderson,Ronald Swanstrom,Barton F. Haynes,Gayathri Athreya,Bette T. Korber,Paul M. Sharp,George M. Shaw,Beatrice H. Hahn +19 more
Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression
Netanya G. Sandler,Netanya G. Sandler,Steven E. Bosinger,Jacob D. Estes,Richard T R Zhu,Gregory K. Tharp,Eli Boritz,Doron Levin,Sathi Wijeyesinghe,Krystelle Nganou Makamdop,Gregory Q. Del Prete,Brenna J. Hill,J. Katherina Timmer,Emma Reiss,Ganit Yarden,Samuel Darko,Eduardo J. Contijoch,John Paul Todd,Guido Silvestri,Martha Nason,Robert B. Norgren,Brandon F. Keele,Srinivas S. Rao,Jerome A. Langer,Jeffrey D. Lifson,Gideon Schreiber,Daniel C. Douek +26 more