Abstract:
:Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine.
journal_name
J Viroljournal_title
Journal of virologyauthors
Verma A,Schmidt BA,Elizaldi SR,Nguyen NK,Walter KA,Beck Z,Trinh HV,Dinasarapu AR,Lakshmanappa YS,Rane NN,Matyas GR,Rao M,Shen X,Tomaras GD,LaBranche CC,Reimann KA,Foehl DH,Gach JS,Forthal DN,Kozlowski PA,Amara RRdoi
10.1128/JVI.01737-19subject
Has Abstractpub_date
2020-02-28 00:00:00issue
6eissn
0022-538Xissn
1098-5514pii
JVI.01737-19journal_volume
94pub_type
杂志文章abstract::The Us11 protein of herpes simplex virus 1 (HSV-1) is an accessory factor with multiple functions. In virus-infected cells, it inhibits double-stranded RNA-dependent protein kinase (PKR), 2',5'-oligoadenylate synthetase, RIG-I, and MDA-5. However, its precise role is incompletely defined. By screening a human cDNA lib...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00402-18
更新日期:2018-06-29 00:00:00
abstract::Equine infectious anemia virus (EIAV) is a lentivirus with in vivo cell tropism primarily for tissue macrophages; however, in vitro the virus can be adapted to fibroblasts and other cell types. Tropism adaptation is associated with both envelope and long terminal repeat (LTR) changes, and findings strongly suggest tha...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.9.5653-5664.2005
更新日期:2005-05-01 00:00:00
abstract::The purpose of this study was to determine whether a cell surface protein that can serve as coreceptor for herpes simplex virus type 1 (HSV-1) entry, herpesvirus entry mediator (previously designated HVEM but renamed HveA), also mediates HSV-1-induced cell-cell fusion. We found that transfection of DNA from KOS-804, a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.7.5802-5810.1998
更新日期:1998-07-01 00:00:00
abstract::Relative to wild-type herpes simplex virus type 1 (HSV-1), ICP0-null mutant viruses reactivate inefficiently from explanted, latently infected mouse trigeminal ganglia (TG), indicating that ICP0 is not essential for reactivation but plays a central role in enhancing the efficiency of reactivation. The validity of thes...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.7.3240-3249.2001
更新日期:2001-04-01 00:00:00
abstract::The rate-limiting steps in infection by human immunodeficiency virus type 1 (HIV-1) deficient in the viral infectivity factor, Vif, are unknown. As a measurement of completion of the early stages of the HIV-1 life cycle, the levels of viral DNA were examined by polymerase chain reaction amplification during infection ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.6322-6326.1993
更新日期:1993-10-01 00:00:00
abstract::Host cell interactions of human adenovirus serotypes belonging to subgroups B (adenovirus type 3 [Ad3] and Ad7) and C (Ad2 and Ad5) were comparatively analyzed at three levels: (i) binding of virus particles with host cell receptors; (ii) cointernalization of macromolecules with adenovirions; and (iii) adenovirus-indu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.8.3661-3673.1990
更新日期:1990-08-01 00:00:00
abstract::Recombinant viruses possessing reporter proteins have been generated for virus research. In the case of the family Flaviviridae, we recently generated recombinant viruses, including the hepatitis C virus of the genus Hepacivirus, Japanese encephalitis virus (JEV) of the genus Flavivirus, and bovine viral diarrhea viru...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01191-19
更新日期:2019-10-29 00:00:00
abstract::Transformation-defective (td) mutants with different sizes of genomic RNA were isolated from the Prague strain of Rous sarcoma virus, subgroup C(PR-C). All six td viruses (tdTYPR-C) isolated from a single UV-irradiated stock of PR-C (clone 2 of TYPR-C) had slightly longer RNA than did the ordinary class b RNA of tdB77...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.2.453-461.1979
更新日期:1979-05-01 00:00:00
abstract::The oncolytic herpes simplex virus (HSV) that has been approved for clinical practice and those HSVs in clinical trials are attenuated viruses, often with the neurovirulence gene γ134.5 and additional genes deleted. One strategy to engineer nonattenuated oncolytic HSVs consists of retargeting the viral tropism to a ca...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00067-17
更新日期:2017-04-28 00:00:00
abstract::Influenza virus particles bind rapidly to vesicular stomatitis, Sindbis, or Rauscher murine leukemia virus particles, forming mixed aggregates demonstrable by electron microscopy. The normal hemagglutinating property of influenza virus is inhibited by these viruses, providing a rapid quantitative assay. Prior treatmen...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.5.1307-1309.1974
更新日期:1974-11-01 00:00:00
abstract::B cells secreting IgG antibodies, but not IgM, are thought to be solely responsible for vaccine-induced protection against rabies virus (RABV) infections in postexposure settings. In this report, we reinvestigated the potential for IgM to mediate protection in a mouse model of RABV vaccination. Immunocompetent mice im...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00995-13
更新日期:2013-08-01 00:00:00
abstract::A tumorigenic line of mouse cells transformed by the nononcogenic murine K papovavirus was established and characterized. Tumor-bearing animals produced antibody specific for K virus-transformed cells; the K virus T antiserum did not react with polyomavirus-transformed cells. Immunoprecipitation of the T antigen in th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.954-956.1984
更新日期:1984-06-01 00:00:00
abstract::Poliovirus proteinase 2A (2Apro) is autocatalytically released from the viral polyprotein by cleavage in cis of a Tyr-Gly dipeptide at its own amino terminus, resulting in separation of the P1 structural and P2-P3 nonstructural protein precursors. A second Ty-Gly dipeptide within 3D polymerase is cleaved by 2Apro in t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.6.3330-3338.1992
更新日期:1992-06-01 00:00:00
abstract::The relative contributions of interleukin-12 (IL-12) and IL-23 to viral pathogenesis have not been extensively studied. IL-12p40 mRNA rapidly increases after neurotropic coronavirus infection. Infection of mice defective in both IL-12 and IL-23 (p40(-/-)), in IL-12 alone (p35(-/-)), and in IL-23 alone (p19(-/-)) revea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00315-09
更新日期:2009-06-01 00:00:00
abstract::Spanins are bacteriophage lysis proteins responsible for disruption of the outer membrane, the final step of Gram-negative host lysis. The absence of spanins results in a terminal phenotype of fragile spherical cells. The phage T1 employs a unimolecular spanin gp11 that has an N-terminal lipoylation signal and a C-ter...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00380-18
更新日期:2018-10-29 00:00:00
abstract:UNLABELLED:Kaposi's sarcoma-associated herpesvirus (KSHV, also called human herpesvirus 8) is linked to the development of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). KSHV expresses several proteins that modulate host cell signaling pathways. One of these proteins...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00511-14
更新日期:2014-08-01 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) lytic infection increases the expression of viral and human interleukin-6 (vIL-6 and hIL-6, respectively), an important factor for cell growth and pathogenesis. Here, we report genome-wide analysis of viral RNA targets of KSHV ORF57 by a novel UV-cross-linking and immunop...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02144-10
更新日期:2011-03-01 00:00:00
abstract::Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting that EBV plays an important role in tumorigenesis. However, the nature of EBV with respect to genome width in vivo and whether EBV undergoes clonal expansion in th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00823-11
更新日期:2011-11-01 00:00:00
abstract::Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fund...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00166-13
更新日期:2013-05-01 00:00:00
abstract::Galectin-9 is a pleiotropic immune modulator affecting numerous cell types of innate and adaptive immunity. Patients with chronic infection with either hepatitis C virus (HCV) or HIV have elevated circulating levels. Limited data exist on the regulation of natural killer (NK) cell function through interaction with gal...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01085-12
更新日期:2013-05-01 00:00:00
abstract::Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) was modified to encode targeting signals known to localize proteins to either the endoplasmic reticulum (ER) or the trans-Golgi network. These motifs conferred the predicted targeting properties on gD in transfected cells as judged by immunofluorescence staini...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9515-9520.1999
更新日期:1999-11-01 00:00:00
abstract::The expression and predicted products of rat c-ros-1 gene, the proto-oncogene of v-ros in UR2 sarcoma virus, were characterized. The c-ros-1 gene was found to be expressed in a tissue-specific manner, and the sizes of its transcripts were heterogeneous: 8.2 kilobases (kb) long in lung and kidney tissues, 6.9 kb in hea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2117-2125.1990
更新日期:1990-05-01 00:00:00
abstract::CD8+ T cells were previously shown to be important in preventing lymphoproliferation and immunodeficiency following infection of murine AIDS (MAIDS)-resistant mice with the LP-BM5 mixture of murine leukemia viruses. To further evaluate the mechanisms contributing to MAIDS resistance, we studied mice lacking CD8+ T cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.3.1808-1813.1997
更新日期:1997-03-01 00:00:00
abstract::The severe acute respiratory syndrome coronavirus (SARS-CoV) encodes numerous accessory proteins whose importance in the natural infection process is currently unclear. One of these accessory proteins is set apart by its function in the context of a related murine hepatitis virus (MHV) infection. SARS-CoV protein 6 in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02406-07
更新日期:2008-07-01 00:00:00
abstract::Mutant recombinant respiratory syncytial viruses (RSV) which cannot express the NS1 and M2-2 proteins, designated rA2DeltaNS1 and rA2DeltaM2-2, respectively, were evaluated as live-attenuated RSV vaccines. The rA2DeltaNS1 virus contains a large deletion that should have the advantageous property of genetic stability d...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.19.9317-9321.2000
更新日期:2000-10-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) Tat protein, which is essential for HIV gene expression and viral replication, is known to mediate pleiotropic effects on various cell functions. For instance, Tat protein is able to regulate the rate of transcription of host cellular genes and to interact with the signa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.13.6846-6854.2004
更新日期:2004-07-01 00:00:00
abstract::Prior studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.6.2740-2751.2000
更新日期:2000-03-01 00:00:00
abstract::Hepatitis B virus (HBV) is an enveloped DNA virus that presumably buds at intracellular membranes of infected cells. HBV budding involves two endocytic host proteins, the ubiquitin-interacting adaptor gamma 2-adaptin and the Nedd4 ubiquitin ligase. Here, we demonstrate that HBV release also requires the cellular machi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00479-07
更新日期:2007-09-01 00:00:00
abstract::Adenovirus class B (Ad3 and Ad7) and class C (Ad1, Ad5, and Ad6) late r-strand mRNA's were found to have segmented 5' leaders. These leaders were very similar among serotype within a class but differed in sequence from the leaders on late mRNA's of a different class. However, the leader components of class B viruses m...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.3.899-912.1979
更新日期:1979-06-01 00:00:00
abstract::Human adenovirus type 12 was propagated on human embryonic kidney cells, and the specific infectivities of intra- and extracellular virus particles were compared between 48 and 104 h after infection. Released virions exhibited a specific infectivity of up to 10 times higher than that of intracellular particles. The in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.55.1.117-125.1985
更新日期:1985-07-01 00:00:00