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Immunization regimens that induce a broadly reactive cytolytic T lymphocyte (CTL) response specific for lentiviral antigens have emerged as the leading candidates in efficacy trials conducted in both animal modelshumans. To date, lentivirus vaccination strategies have overlooked one such immunization strategy, namely the use of particulate antigens. To evaluate the efficacy of targeting antigen into...
Influenza A (H5N1) viruses infected humans in Hong Kong between May and December, 1997. Sixteen viruses, including 6 from fatal cases, were isolated during this outbreak. Molecular analysis of the surface proteins genes encoding the hemagglutinin (HA) and neuraminidase (NA) of these H5N1 isolates, of a subtype not previously known to infect humans, are presented. The 16 human H5 HA sequences contain...
Alphaherpesviral glycoprotein D (gD) is a critical component of the cell membrane penetration system. Cells that express gD of herpes simplex virus type 1 (HSV1), pseudorabies virus (PRV), or bovine herpesvirus type 1.1 (BHV1.1) resist infection by the homologous virus due to interference with viral entry at the level of penetration. BHV1.1 gD interferes with the distantly related viruses HSV1 and...
Antisera were raised against peptides corresponding to the N-termini of capsid proteins VP1 and VP2 from the parvovirus minute virus of mice. Epitopes in the 142-amino-acid VP1-specific region were not accessible in the great majority of newly released viral particles, and sera directed against them failed to neutralize virus directly or deplete stocks of infectious virions. However, brief exposure...
Antibodies (Abs) can contribute to the cure of a viral infection, in principle, in two ways by: (1) binding to infected cells and thereby reducing the production of progeny virus [here termed cell-targeting (CT) activity] and (2) reacting with released progeny virus and thereby inhibiting the spread of the infection [termed virus neutralizing (VN) activity]. We have previously shown that a pulmonary...
The influenza A virus M 2 integral membrane protein is an ion channel that permits protons to enter virus particles during uncoating of virions in endosomes, and it also modulates the pH of thetrans-Golgi network in virus-infected cells. M 2 protein is a homo-oligomer of 97 residues with a single transmembrane (TM) domain whose residues encompass the pore region of the channel and...
Three rhesus macaques were infected with an SIVmac239 variant containing substitutions of 73/74PA→ED and 204D→R in Nef that disrupted the ability of Nef to downregulate CD4 surface expression. One of these animals, Mm8155, rapidly progressed to AIDS and died 21 weeks postinfection. During the final 5 weeks of infection, the levels of viral RNA and of p27 antigenemia were about 100-fold higher than...
Groundnut rosette disease is caused by a complex of agents comprising groundnut rosette umbravirus (GRV), GRV satellite RNA (sat-RNA)groundnut rosette assistor luteovirus (GRAV). Both GRAV and GRV sat-RNA are needed for GRV to be aphid transmissible. To understand the role of GRAVGRV sat-RNA in the aphid transmission of GRV, encapsidation of GRV genomicsatellite RNAs has been studied using transgenicNicotiana...
The mechanism of homologous recombination has been studied previously in brome mosaic virus (BMV), a tricomponent, positive-stranded RNA virus of plants, by using artificial sequences (reviewed by J. J. BujarskiP. D. Nagy (1996).Semin. Virol.7, 363–372). Here we extend these studies over BMV-derived sequences to obtain clues on prediction of homologous recombination hot spots. First, mismatch mutations,...
Protein–protein interactions of the p24 (HIV-1) capsid protein play an essential role in the production of infectious virus particles. To map the putative p24 dimerization site, a set of overlapping peptides spanning the p24 sequence was prepared using spot synthesis on a cellulose membrane and probed with recombinant p24 (rp24). Three sequence regions interacting with rp24 were identified. Peptides...
The PKR protein kinase is an important regulator of viral mRNA translation. A ∼50-kb gene (Pkr) encodes the human PKR protein that is inducible by interferon (IFN). ThePkrpromoter region has a novel 15-bp DNA element designated as KCS required for transcriptional activity that is located 4 bp upstream of a 13-bpIFN-stimulatedresponseelement (ISRE) that confers inducibility by type I IFN. We have carried...
The initiation of reverse transcription of human immunodeficiency virus type 1 (HIV-1) exclusively utilizes tRNA Lys,3 as a primer. Previous studies have shown that HIV-1 could use alternative tRNAs, such as tRNA Ile or tRNA His , to initiate reverse transcription only if the primer binding site (PBS) was made complementary to the 3′ terminal 18 nucleotides of the cognate tRNA...
The genes encoding the respiratory syncytial virus (RSV) attachment (G) and fusion (F) envelope glycoproteins were expressed separately as additional genes in recombinant vesicular stomatitis viruses (VSV). Cells infected with the VSV-RSV F recombinant formed large syncytia illustrating the fusion activity of F in absence of other RSV proteins. Both F and G glycoproteins were expressed at the cell...
The infection mechanism of vaccinia virus is largely unknown. Neither the attachment protein of extracellular enveloped virus (EEV), the biologically relevant infectious form of the virus, nor its cellular receptor has been identified. Surprisingly, all former attempts using antibodies to block EEV infection of cellsin vitrohad failed. Here, we report the production of an anti-envelope hyperimmune...
Heterosubtypic immunity, defined as cross-reactive immune responses to influenza virus of a different serotype than the virus initially encountered, was investigated in association with virus-specific cytotoxic T lymphocyte (CTL) responses induced in systemic and mucosa-associated lymph nodes after immunization via different routes. Mice immunized by the pulmonary route with live nonpathogenic influenza...
Vaccinia virus (VV) encodes a 37-kDa envelope protein (p37) that is palmitylated on cysteine residues 185186 of the 372-amino acid protein. We have previously reported on a loosely conserved consensus motif. Further analysis has identified a conserved consensus sequence, Hydro*AAC(C)A(Hydro* represents a hydrophobic portion of a protein determined by any one of the following: a hydrophobic sequence,...
The fusion (F) protein of the paramyxovirus SV5 contains two heptad repeat regions, HRA adjacent to the fusion peptide and HRB proximal to the transmembrane domain. Peptides, N-1 and C-1, respectively, corresponding to these heptad repeat regions form a thermostable, α-helical trimer of heterodimers (S. B. Joshi, R. E. Dutch, and R. A. Lamb (1998).Virology 248,20–34). Further characterization of the...
Adenovirus 12 (Ad12), but not adenovirus 2 or 5, induces metaphase chromosome fragility at four specific loci in humans:RNU1, RNU2, PSU1,andRN5S.As each of these sites corresponds to a tandemly repeated multigene family encoding a small, abundant structural RNA, we proposed that Ad12 hinders metaphase chromatin condensation, interfering either directly or indirectly with transcriptional regulation...
The hypothesis that the enteric bovine calici-like virus Newbury agent (NA-2) belongs to the familyCaliciviridaewas examined by genome sequence analysis. Use of solid-phase immune electron microscopy allowed samples with good levels of virus to be identified and amplification of the genome was achieved by reverse transcription–polymerase chain reaction. Examination of a 216-amino-acid sequence in...
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