Abstract:
UNLABELLED:CD4+ T cells play a pivotal role in the control of chronic viral infections. Recently, nontraditional CD4+ T cell functions beyond helper effects have been described, and a role for cytolytic CD4+ T cells in the control of HIV infection has been suggested. We define here the transcriptional, phenotypic, and functional profiles of HIV-specific cytolytic CD4+ T cells. Fluidigm BioMark and multiparameter flow cytometric analysis of HIV-specific cytolytic CD4+ T cells revealed a distinct transcriptional signature compared to Th1 CD4+ cells but shared similar features with HIV-specific cytolytic CD8+ T cells. Furthermore, HIV-specific cytolytic CD4+ T cells showed comparable killing activity relative to HIV-specific CD8+ T cells and worked cooperatively in the elimination of virally infected cells. Interestingly, we found that cytolytic CD4+ T cells emerge early during acute HIV infection and tightly follow acute viral load trajectory. This emergence was associated to the early viral set point, suggesting an involvement in early control, in spite of CD4 T cell susceptibility to HIV infection. Our data suggest cytolytic CD4+ T cells as an independent subset distinct from Th1 cells that show combined activity with CD8+ T cells in the long-term control of HIV infection. IMPORTANCE:The ability of the immune system to control chronic HIV infection is of critical interest to both vaccine design and therapeutic approaches. Much research has focused on the effect of the ability of CD8+ T cells to control the virus, while CD4+ T cells have been overlooked as effectors in HIV control due to the fact that they are preferentially infected. We show here that a subset of HIV-specific CD4+ T cells cooperate in the cytolytic control of HIV replication. Moreover, these cells represent a distinct subset of CD4+ T cells showing significant transcriptional and phenotypic differences compared to HIV-specific Th1 cells but with similarities to CD8+ T cells. These findings are important for our understanding of HIV immunopathology.
journal_name
J Viroljournal_title
Journal of virologyauthors
Johnson S,Eller M,Teigler JE,Maloveste SM,Schultz BT,Soghoian DZ,Lu R,Oster AF,Chenine AL,Alter G,Dittmer U,Marovich M,Robb ML,Michael NL,Bolton D,Streeck Hdoi
10.1128/JVI.00438-15subject
Has Abstractpub_date
2015-08-01 00:00:00pages
7494-505issue
15eissn
0022-538Xissn
1098-5514pii
JVI.00438-15journal_volume
89pub_type
杂志文章abstract::Herpes simplex virus 1 (HSV-1) capsids leave the nucleus by a process of envelopment and de-envelopment at the nuclear envelope (NE) that is accompanied by structural alterations of the NE. As capsids translocate across the NE, transient primary enveloped virions form in the perinuclear space. Here, we provide evidenc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05314-11
更新日期:2011-10-01 00:00:00
abstract::To assess the heterogeneity of cytotoxic T lymphocytes (CTLs) directed against viral epitopes, we studied six class I major histocompatibility complex-restricted (H-2Db) CTL clones that recognize the same 9-amino-acid immunodominant epitope, amino acids 278 to 286 from envelope glycoprotein 2 (GP2) of lymphocytic chor...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.5.1845-1851.1989
更新日期:1989-05-01 00:00:00
abstract::Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) disease is associated with an increased viral burden in the peripheral blood and a loss of circulating CD4+ T cells. HIV-1 isolates obtained prior to this stage of disease often have a "slow-low," non-syncytium-inducing (NSI) phenotype, whereas thos...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.12.8188-8192.1994
更新日期:1994-12-01 00:00:00
abstract::Virus-infected cells secrete a broad range of interferons (IFN) which confer resistance to yet uninfected cells by triggering the synthesis of antiviral factors. The relative contributions of the various IFN subtypes to innate immunity against virus infections remain elusive. IFN-alpha, IFN-beta, and other type I IFN ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00272-10
更新日期:2010-06-01 00:00:00
abstract::Cell surface receptors exploited by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) for infection are major determinants of tropism. HIV-1 usually requires two receptors to infect cells. Gp120 on HIV-1 virions binds CD4 on the cell surface, triggering conformational rearrangements that creat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.9.7795-7804.1999
更新日期:1999-09-01 00:00:00
abstract::The catalytic core domain (CCD) of human immunodeficiency virus type 1 (HIV-1) integrase (IN) harbors the enzyme active site and binds viral and chromosomal DNA during integration. Thirty-five CCD mutant viruses were constructed, paying particular attention to conserved residues in the Phe(139)-Gln(146) flexible loop ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.4.2493-2505.2005
更新日期:2005-02-01 00:00:00
abstract::Egress of wrapped virus (WV) to the cell periphery following vaccinia virus (VACV) replication is dependent on interactions with the microtubule motor complex kinesin-1 and is mediated by the viral envelope protein A36. Here we report that ectromelia virus (ECTV), a related orthopoxvirus and the causative agent of mou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06636-11
更新日期:2012-07-01 00:00:00
abstract::ICP0, an alpha (immediate-early) protein of herpes simplex virus 1, performs at least two key functions. It blocks inhibition of viral-gene expression by interferon, a function dependent on the degradation of the ND10 components PML and SP100 by the ubiquitin ligase expressed by the RING finger (RF), and it blocks sil...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01940-08
更新日期:2009-01-01 00:00:00
abstract::Human cytomegalovirus (HCMV) UL84 is a phosphoprotein that shuttles from the nucleus to the cytoplasm and is required for oriLyt-dependent DNA replication and viral growth. UL84 was previously shown to interact with IE2 (IE86) in infected cells, and this interaction down-regulates IE2-mediated transcriptional activati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01559-07
更新日期:2008-01-01 00:00:00
abstract::The signaling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02255-16
更新日期:2017-03-13 00:00:00
abstract::Acute measles in children can be prevented by immunization with the live attenuated measles vaccine virus. Although immunization is able to induce CD4 and CD8 T cells as well as neutralizing antibodies, only the latter have been correlated with protective immunity. CD8 T cells, however, have been documented to be impo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00160-07
更新日期:2007-08-01 00:00:00
abstract::The small RNA segment (S segment) of Uukuniemi (UUK) virus encodes two proteins, the nucleocapsid protein (N) and a nonstructural protein (NSs), by an ambisense strategy. The function of NSs has not been elucidated for any of the bunyaviruses expressing this protein. We have now expressed the N and NSs proteins in Sf9...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4233-4241.1992
更新日期:1992-07-01 00:00:00
abstract:UNLABELLED:Hepatitis B virus (HBV) infects hundreds of millions of people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV is an enveloped virus with a relaxed circular (RC) DNA genome. In the nuclei of infected human hepatocytes, conversion of RC DNA from the incoming viri...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01263-15
更新日期:2015-10-21 00:00:00
abstract::Phenol-extracted, infectious deoxyribonucleic acid (DNA) species from phi105 phage particles, from phi105 lysogenic bacteria, and from induced phi105 lysogenic bacteria were sedimented in sucrose gradients. Infectious DNA from phi105 particles sedimented like the bulk of mature phage DNA in neutral sucrose. Infectivit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.5.5.604-608.1970
更新日期:1970-05-01 00:00:00
abstract::Recombinant interleukin-16 (rIL-16) has been found to inhibit human immunodeficiency virus type 1 (HIV-1) replication in acutely or endogenously infected CD4(+) T cells. However, the effect of rIL-16 on HIV-1 replication in antigen-presenting cells (APCs) is still unknown. We show here a potent HIV-suppressive activit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.8.7008-7013.1999
更新日期:1999-08-01 00:00:00
abstract::Serial passage of reovirus temperature-sensitive (ts) mutant C(447) produced by passage 9 (P9) a heavily defective population of virus from which the double-stranded RNA genomic segments L(1), L(3), and M(1) were largely missing. Viral cores obtained from this P9 population were heterogeneous with respect to buoyant d...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.23.2.250-262.1977
更新日期:1977-08-01 00:00:00
abstract::Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02138-16
更新日期:2017-01-18 00:00:00
abstract::Complexes of f2 phage RNA and its A protein, or maturation protein, transfect Escherichia coli cells much better than does protein-free RNA. We used these complexes to introduce the bacteriophage f2 lysis gene into cells. The A protein-RNA complex was found to kill cells, probably by causing them to leak large macromo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.39.1.60-66.1981
更新日期:1981-07-01 00:00:00
abstract::Moloney murine leukemia virus (M-MuLV) and M-MuLV-derived retroviral vectors are not expressed in early mouse embryos or in embryonal carcinoma cells. M-MuLV-derived mutants or M-MuLV-related variants which transduce the neomycin phosphotransferase gene can, however, induce drug resistance in embryonal carcinoma cells...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.9.2742-2746.1987
更新日期:1987-09-01 00:00:00
abstract::Immature retroviral particles are assembled by self-association of the structural polyprotein precursor Gag. During maturation the Gag polyprotein is proteolytically cleaved, yielding mature structural proteins, matrix (MA), capsid (CA), and nucleocapsid (NC), that reassemble into a mature viral particle. Proteolytic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05564-11
更新日期:2012-02-01 00:00:00
abstract::Recombination is one of the driving forces of viral evolution. RNA recombination events among similar RNA viruses are frequent, although RNA recombination could also take place among unrelated viruses. In this paper, we have established efficient interviral recombination systems based on yeast and plants. We show that...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01015-19
更新日期:2019-12-12 00:00:00
abstract::In this study, we document that efficient interaction between arenavirus nucleoprotein (NP) and RNA-dependent RNA polymerase (L protein), the two trans-acting viral factors required for both virus RNA replication and gene transcription, requires the presence of virus-specific RNA sequences located within the untransla...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00103-15
更新日期:2015-05-01 00:00:00
abstract::Differentiating infected from vaccinated animals (DIVA) strategies have been central enabling techniques in several successful viral disease elimination programs. However, owing to their long and uncertain development process, no DIVA-compatible vaccines are available for many important diseases. We report herein a ne...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01573-19
更新日期:2020-02-28 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 RNA-dependent RNA polymerase (NS5B) of hepatitis C virus (HCV) is an unusually attractive target for drug discovery since it contains five distinct drugable sites. The success of novel antiviral therapies will require nonnucleoside inhibitors to be active in at least patients infected with HCV of subtypes 1a and 1...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01980-09
更新日期:2010-03-01 00:00:00
abstract::Influenza A H9N2 viruses are common poultry pathogens that occasionally infect swine and humans. It has been shown previously with H9N2 viruses that reassortment can generate novel viruses with increased transmissibility. Here, we demonstrate the modeling power of a novel transfection-based inoculation system to selec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02677-13
更新日期:2014-01-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) encodes specific trafficking signals within its long cytoplasmic tail (CT) that regulate incorporation into HIV-1 particles. Rab11-family interacting protein 1C (FIP1C) and Rab14 are host trafficking factors required for Env particle incorpora...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01893-17
更新日期:2018-02-12 00:00:00
abstract::To analyze proteolytic processing of foamy (spuma) retroviruses, two mutations were generated in the presumed active-site triplet Asp-Ser-Gly in the predicted proteinase (PR) region of the human foamy virus (HSRV). The mutations changed either the presumed catalytic aspartic acid residue to a catalytically incompetent...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.11.7264-7268.1995
更新日期:1995-11-01 00:00:00
abstract::Porcine reproductive and respiratory syndrome virus (PRRSV) is a recently described arterivirus responsible for disease in swine worldwide. Comparative sequence analysis of 3'-terminal structural genes of the single-stranded RNA viral genome revealed the presence of two genotypic classes of PRRSV, represented by the p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.1.270-280.1999
更新日期:1999-01-01 00:00:00
abstract::Current knowledge of human immunodeficiency virus type 1 envelope (Env) glycoprotein structure and function is based on studies of clade B viruses. We present evidence of sequence and structural differences in viral glycoprotein gp120 between clades B and C. In clade C, the C3 region alpha2-helix exhibits high sequenc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01954-06
更新日期:2007-05-01 00:00:00