Abstract:
:In clinical trials, HIV-1 broadly neutralizing antibodies (bnAbs) effectively lower plasma viremia and delay virus reemergence. The presence of less neutralization-susceptible strains prior to treatment decreases the efficacy of these antibody-based treatments, but neutralization sensitivity often cannot be predicted by sequence analysis alone. We found that phenotypically confirmed CXCR4-utilizing strains are less neutralization sensitive, especially to variable loop 3 (V3 loop)-directed bnAbs, than exclusively CCR5-utilizing strains in some, but not all, cases. Homology modeling suggested that the primary V3 loop bnAb epitope is equally accessible among CCR5- and CXCR4-using strains, although variants that exclusively use CXCR4 have V3 loop protrusions that interfere with CCR5 receptor interactions. Homology modeling also showed that among some, but not all, envelopes with decreased neutralization sensitivity, V1 loop orientation interfered with V3 loop-directed bnAb binding. Thus, there are likely different structural reasons for the coreceptor usage restriction and the different bnAb susceptibilities. Importantly, we show that individuals harboring envelopes with higher likelihood of using CXCR4 or greater predicted V1 loop interference have faster virus rebound and a lower maximum decrease in plasma viremia, respectively, after treatment with a V3 loop bnAb. Knowledge of receptor usage and homology models may be useful in developing future algorithms that predict treatment efficacy with V3 loop bnAbs.IMPORTANCE The efficacy of HIV-1 broadly neutralizing antibody (bnAb) therapies may be compromised by the preexistence of less susceptible variants. Sequence-based methods are needed to predict pretreatment variants' neutralization sensitivities. HIV-1 strains that exclusively use the CXCR4 receptor rather than the CCR5 receptor are less neutralization susceptible, especially to variable loop 3 (V3 loop) bnAbs in some, but not all, instances. While the inability to utilize the CCR5 receptor maps to a predicted protrusion in the envelope V3 loop, this viral determinant does not directly influence V3 loop bnAb sensitivity. Homology modeling predicts that contact between the envelope V1 loop and the antibody impacts V3 loop bnAb susceptibility in some cases. Among pretreatment envelopes, increased probability of using CXCR4 and greater predicted V1 interference are associated with faster virus rebound and a smaller decrease in the plasma virus level, respectively, after V3 loop bnAb treatment. Receptor usage information and homology models may be useful for predicting V3 loop bnAb therapy efficacy.
journal_name
J Viroljournal_title
Journal of virologyauthors
Registre L,Moreau Y,Ataca ST,Pulukuri S,Henrich TJ,Lin N,Sagar Mdoi
10.1128/JVI.01604-19subject
Has Abstractpub_date
2020-01-06 00:00:00issue
2eissn
0022-538Xissn
1098-5514pii
JVI.01604-19journal_volume
94pub_type
杂志文章abstract::The latency-related (LR) gene of bovine herpesvirus 1 (BHV-1) is abundantly expressed during latency. A mutant BHV-1 strain that contains three stop codons at the 5' terminus of the LR gene (LR mutant) does not reactivate from latency. This study demonstrates that the LR mutant does not express open reading frame 2 or...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.6.3184-3189.2004
更新日期:2004-03-01 00:00:00
abstract::Porcine epidemic diarrhea coronavirus (PEDV) has significantly damaged America's pork industry. Here we investigate the receptor usage and cell entry of PEDV. PEDV recognizes protein receptor aminopeptidase N from pig and human and sugar coreceptor N-acetylneuraminic acid. Moreover, PEDV infects cells from pig, human,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00430-15
更新日期:2015-06-01 00:00:00
abstract::The genome RNA and six mRNA species of infectious hematopoietic necrosis virus were analyzed by denaturing gel electrophoresis. The following molecular weights were determined: genome RNA, 3.7 X 10(6); mRNA 1, 2.26 X 10(6); mRNA 2, 5.63 X 10(5); mRNA 3, 4.84 X 10(5); mRNA 4 (containing two different mRNA species), 3.0...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.2.462-468.1985
更新日期:1985-02-01 00:00:00
abstract:UNLABELLED:Foamy viruses (FVs) are complex retroviruses that establish lifelong persistent infection without evident pathology. However, the roles of cellular factors in FV latency are poorly understood. This study revealed that N-Myc interactor (Nmi) could inhibit the replication of prototype foamy virus (PFV). Overex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00799-14
更新日期:2014-06-01 00:00:00
abstract::Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Both noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be isolated from persistently infected cattle suffering from the lethal mucosal disease. The cp biot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.10.4692-4698.2001
更新日期:2001-05-01 00:00:00
abstract::Clones of virogenic simian virus 40 (SV40)-transformed hamster kidney cells were exposed to medium deficient in the essential amino acids leucine, arginine, or methionine. Infectious virus was induced after deprivation periods of from 24 to 32 hr. The highest yields of infectious SV40 were obtained from cultures depri...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.3.448-453.1972
更新日期:1972-03-01 00:00:00
abstract::ICP0 is a transcriptional activating protein required for the efficient replication and reactivation of latent herpes simplex virus 1 (HSV-1). Multiple regions of ICP0 contribute its activity, the most prominent of which appears to be the RING finger, which confers E3 ubiquitin ligase activity. A region in the C termi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02265-10
更新日期:2011-05-01 00:00:00
abstract::The agent(s) responsible for sporadic non-A, non-B hepatitis in humans was serially transmitted in rhesus monkeys by intravenous inoculation of the stool extract from a patient. A novel agent called HFV (hepatitis French [origin] virus) was present as 27- to 37-nm particles in the infectious stool extract. Hepatopathi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.12.7810-7815.1994
更新日期:1994-12-01 00:00:00
abstract::The first morphological evidence of African swine fever virus (ASFV) assembly is the appearance of precursor viral membranes, thought to derive from the endoplasmic reticulum, within the assembly sites. We have shown previously that protein p54, a viral structural integral membrane protein, is essential for the genera...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00600-10
更新日期:2010-08-01 00:00:00
abstract::Numerous deaths of koi and common carp (Cyprinus carpio) were observed on many farms throughout Israel, resulting in severe financial losses. The lethal viral disease observed is highly contagious and extremely virulent, but morbidity and mortality are restricted to koi and common carp populations. Diseased fish exhib...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.4.1983-1991.2005
更新日期:2005-02-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) evokes a strong immune response, but the virus persists. Polymorphisms within known antigenic sites result in loss of immune recognition and can be positively selected. Amino acid variation outside known HLA class I restricted epitopes can also enable immune escape by interf...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00968-06
更新日期:2007-02-01 00:00:00
abstract::A covalently closed circular form of unintegrated viral DNA obtained from NIH 3T3 cells freshly infected with Moloney murine leukemia virus (M-MLV) and a port of the endogenous M-MLV from the BALB/Mo mouse strain have been cloned in bacteriophage lambda. The unintegrated viral DNA was cleaved with restriction endonucl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.1.254-263.1980
更新日期:1980-10-01 00:00:00
abstract::The induction of an interferon-induced antiviral state is a powerful cellular response against viral infection that limits viral spread. Here, we show that a preexisting antiviral state inhibits the replication of influenza A viruses in human A549 cells by preventing transport of the viral genome to the nucleus and th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02220-13
更新日期:2013-12-01 00:00:00
abstract::Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins are encapsidated by assembling HIV-1 virions and edit viral cDNA in the next round of infection. Using alpha interferon (IFN-α)-treated monocyte-derived macrophages, we show that infrequent editing of HIV-1 reverse transcripts can als...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00775-11
更新日期:2011-12-01 00:00:00
abstract::Homozygous human immunodeficiency virus type 1 (HIV-1)-transgenic mice (Tg26) appear normal at birth but die within 3 to 4 weeks. The skin of these animals shows diffuse scaling and high-level expression of both HIV-1 mRNA and gp120. Previous experiments showed that treatment with human chorionic gonadatropin (hCG) pr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.22.11710-11714.2002
更新日期:2002-11-01 00:00:00
abstract::We have previously designed in vitro model systems to characterize the herpes simplex virus type 1 (HSV-1) genome during in vitro virus latency. Latency was established by treatment of infected human embryo lung fibroblast (HEL-F) cells or rat fetal neurons with (E)-5-(2-bromovinyl)-2'-deoxyuridine and human leukocyte...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.1.205-213.1984
更新日期:1984-01-01 00:00:00
abstract:UNLABELLED:An understanding of the antigen-specific B-cell response to the influenza virus hemagglutinin (HA) is critical to the development of universal influenza vaccines, but it has not been possible to examine these cells directly because HA binds to sialic acid (SA) on most cell types. Here, we use structure-based...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03422-13
更新日期:2014-04-01 00:00:00
abstract::A cyanophage, PaV-LD, has been isolated from harmful filamentous cyanobacterium Planktothrix agardhii in Lake Donghu, a shallow freshwater lake in China. Here, we present the cyanophage's genomic organization and major structural proteins. The genome is a 95,299-bp-long, linear double-stranded DNA and contains 142 pot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.06282-11
更新日期:2012-01-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) DNA and RNA have been detected in peripheral nervous system (PNS) and central nervous system (CNS) tissues of latently infected mice. However, explant methods are successful in reactivating HSV-1 only from latently infected PNS tissues. In this report, latent herpesvirus infections ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.3.749-756.1988
更新日期:1988-03-01 00:00:00
abstract::The herpes simplex virus (HSV) heterodimer gE/gI and another membrane protein, US9, which has neuron-specific effects, promote the anterograde transport of virus particles in neuronal axons. Deletion of both HSV gE and US9 blocks the assembly of enveloped particles in the neuronal cytoplasm, which explains why HSV vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01113-20
更新日期:2020-11-09 00:00:00
abstract::We have identified a trans-dominant mutant form of the herpes simplex virus (HSV) DNA-binding protein ICP8 which inhibits viral replication. When expressed by the V2.6 cell line, the mutant gene product inhibited wild-type HSV production by 50- to 150-fold when the multiplicity of infection was less than 5. Production...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.5.2666-2675.1991
更新日期:1991-05-01 00:00:00
abstract::The amino-terminal region of the Vif molecule in human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus (SIV) contains a conserved SLV/Ix4Yx9Y motif that was first described in 1992, but the importance of this motif for Vif function has not yet been examined. Our characterization of the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00653-09
更新日期:2009-09-01 00:00:00
abstract::Wild-type clones of reovirus serotypes 1 (Lang), 2 (Jones), and 3 (Dearing) were serially passaged in L cells at a high multiplicity of infection, and the virus population was examined at passage levels 2, 5, and 11 for the presence of temperature-sensitive (ts) mutants. By passage 11 all three serotypes contained ts ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.34.1.285-287.1980
更新日期:1980-04-01 00:00:00
abstract::We have evaluated the potential of conferring protective immunity to herpes simplex virus type 2 (HSV-2) by selectively inducing an HSV-specific CD8(+) cytotoxic T-lymphocyte (CTL) response directed against a single major histocompatibility complex class I-restricted CTL recognition epitope. We generated a recombinant...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.9567-9574.1998
更新日期:1998-12-01 00:00:00
abstract::Three double-stranded RNA segments of bacteriophage phi 6 (L, M, and S) were transcribed in vitro by a virion-associated RNA polymerase. Regulation of L transcription was distinct from regulation of M and S transcription. Transcription of the L segment, which codes for early proteins, required manganous ion and high c...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.1.196-203.1983
更新日期:1983-04-01 00:00:00
abstract::The involvement of the mouse mammary tumor virus (MTV) in spontaneous and hormone-induced mammary tumors in low-mammary-tumor mouse strains was studied by comparing the amounts of MTV RNA and MTV DNA sequences in mammary tumors and other tissues of mice with an without hormonal treatments. The following results were o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.27.3.551-559.1978
更新日期:1978-09-01 00:00:00
abstract::Beyond their role in cellular RNA metabolism, DExD/H-box RNA helicases are hijacked by various RNA viruses in order to assist replication of the viral genome. Here, we identify the DExH-box RNA helicase 9 (DHX9) as a binding partner of chikungunya virus (CHIKV) nsP3 mainly interacting with the C-terminal hypervariable...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01764-18
更新日期:2019-02-05 00:00:00
abstract::Reovirus infection of the murine spinal cord (SC) was used as a model system to investigate innate immune responses during viral myelitis, including the activation of glia (microglia and astrocytes) and interferon (IFN) signaling and increased expression of inflammatory mediators. Reovirus myelitis was associated with...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00171-12
更新日期:2012-08-01 00:00:00
abstract::Parvoviruses infect humans and a broad range of animals, from mammals to crustaceans, and generally are associated with a variety of acute and chronic diseases. However, many others cause persistent infections and are not known to be associated with any disease. Viral persistence is likely related to the ability to in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00828-11
更新日期:2011-10-01 00:00:00
abstract::The antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV), a member of the family Flaviviridae, were investigated in this study. In vitro, inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine macrophages was correlated to cellular NO production. When cocultured with inf...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.7.5227-5235.1997
更新日期:1997-07-01 00:00:00