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排序方式: 共有206条查询结果,搜索用时 15 毫秒
81.
Protection of Macaca nemestrina from disease following pathogenic simian immunodeficiency virus (SIV) challenge: utilization of SIV nucleocapsid mutant DNA vaccines with and without an SIV protein boost 总被引:1,自引:0,他引:1 下载免费PDF全文
Gorelick RJ Benveniste RE Lifson JD Yovandich JL Morton WR Kuller L Flynn BM Fisher BA Rossio JL Piatak M Bess JW Henderson LE Arthur LO 《Journal of virology》2000,74(24):11935-11949
Molecular clones were constructed that express nucleocapsid (NC) deletion mutant simian immunodeficiency viruses (SIVs) that are replication defective but capable of completing virtually all of the steps of a single viral infection cycle. These steps include production of particles that are viral RNA deficient yet contain a full complement of processed viral proteins. The mutant particles are ultrastructurally indistinguishable from wild-type virus. Similar to a live attenuated vaccine, this approach should allow immunological presentation of a full range of viral epitopes, without the safety risks of replicating virus. A total of 11 Macaca nemestrina macaques were inoculated with NC mutant SIV expressing DNA, intramuscularly (i.m.) in one study and i.m. and subcutaneously in another study. Six control animals received vector DNA lacking SIV sequences. Only modest and inconsistent humoral responses and no cellular immune responses were observed prior to challenge. Following intravenous challenge with 20 animal infectious doses of the pathogenic SIV(Mne) in a long-term study, all control animals became infected and three of four animals developed progressive SIV disease leading to death. All 11 NC mutant SIV DNA-immunized animals became infected following challenge but typically showed decreased initial peak plasma SIV RNA levels compared to those of control animals (P = 0.0007). In the long-term study, most of the immunized animals had low or undetectable postacute levels of plasma SIV RNA, and no CD4(+) T-cell depletion or clinical evidence of progressive disease, over more than 2 years of observation. Although a subset of immunized and control animals were boosted with SIV(Mne) proteins, no apparent protective benefit was observed. Immunization of macaques with DNA that codes for replication-defective but structurally complete virions appears to protect from or at least delay the onset of AIDS after infection with a pathogenic immunodeficiency virus. With further optimization, this may be a promising approach for vaccine development. 相似文献
82.
Nonparametric regression in the presence of measurement error 总被引:4,自引:0,他引:4
83.
A model of prebiotic replication discussed by Szathmary and Maynard Smith (1997) is refined in accordance with Lifson's (1997) theory on the crucial stages in the origin of animate matter. The refined model accounts for two processes associated with replication: (1) Replicators always decompose at some rate. (2) Replicators deplete their reactants at a rate equal to the rate of their own replication. Consequently, replicators and their reactants are linked by a non-linear feedback process that keeps them within limits and leads them toward a steady state. The model suggests that: (a) All competing replicators, including those which replicate at sub-exponential "parabolic" and super-exponential "hyperbolic" rates, are subject to natural selection. (b) Survival/extinction is determined by positive/negative net-replication irrespective of the mechanism of replication. (c) Being fit/unfit is the consequence of survival/extinction rather than its cause. In other words, natural selection and survival of the fit is the outcome of continual extinction of the unfit. 相似文献
84.
Highly attenuated vaccine strains of simian immunodeficiency virus protect against vaginal challenge: inverse relationship of degree of protection with level of attenuation 总被引:7,自引:0,他引:7 下载免费PDF全文
Johnson RP Lifson JD Czajak SC Cole KS Manson KH Glickman R Yang J Montefiori DC Montelaro R Wyand MS Desrosiers RC 《Journal of virology》1999,73(6):4952-4961
Three different deletion mutants of simian immunodeficiency virus (SIV) that vary in their levels of attenuation were tested for the ability to protect against mucosal challenge with pathogenic SIV. Four female rhesus monkeys were vaccinated by intravenous inoculation with SIVmac239Delta3, four with SIVmac239Delta3X, and four with SIVmac239Delta4. These three vaccine strains exhibit increasing levels of attenuation: Delta3 < Delta3X 相似文献
85.
High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis 下载免费PDF全文
Zink MC Suryanarayana K Mankowski JL Shen A Piatak M Spelman JP Carter DL Adams RJ Lifson JD Clements JE 《Journal of virology》1999,73(12):10480-10488
AIDS dementia and encephalitis are complications of AIDS occurring most frequently in patients who are immunosuppressed. The simian immunodeficiency virus (SIV) model used in this study was designed to reproducibly induce AIDS in macaques in order to examine the effects of a neurovirulent virus in this context. Pigtailed macaques (Macaca nemestrina) were coinoculated with an immunosuppressive virus (SIV/DeltaB670) and a neurovirulent molecularly cloned virus (SIV/17E-Fr), and more than 90% of the animals developed moderate to severe encephalitis within 6 months of inoculation. Viral load in plasma and cerebrospinal fluid (CSF) was examined longitudinally to onset of AIDS, and viral load was measured in brain tissue at necropsy to examine the relationship of systemic and central nervous system (CNS) viral replication to the development of encephalitis. In all animals, plasma viral load peaked at 10 to 14 days postinfection and remained high throughout infection with no correlation found between plasma viremia and SIV encephalitis. In contrast, persistent high levels of CSF viral RNA after the acute phase of infection correlated with the development of encephalitis. Although high levels of viral RNA were found in the CSF of all macaques (six of six) during the acute phase, this high level was maintained only in macaques developing SIV encephalitis (five of six). Furthermore, the level of both viral RNA and antigen in the brain correlated with the severity of the CNS lesions. The single animal in this group that did not have CNS lesions had no detectable viral RNA in any of the regions of the brain. The results substantiate the use of CSF viral load measurements in the postacute phase of SIV infection as a marker for encephalitis and CNS viral replication. 相似文献
86.
A characteristic feature of the sperm P1 protamines of eutherian mammals is
the constant presence of six to nine cysteine residues per molecule. During
spermiogenesis these residues become oxidized to form a three-dimensional
network of disulfide bridges between, and within, protamine molecules in
the sperm chromatin. This covalent cross linking strongly stabilizes
eutherian sperm nuclei. In contrast, protamines sequenced from teleost
fish, birds, monotremes, and marsupials all lack cysteine residues and
their sperm nuclei, without the stabilizing cross links, are easily
decondensed in vitro. We have now found that one genus of tiny, shrewlike
dasyurid marsupials, the Planigales, possess P1 protamines containing five
to six cysteine residues. These residues appear to have evolved since the
divergence of Planigales from other members of the family Dasyuridae, such
as the marsupial mouse, Sminthopsis crassicaudata. We believe this
constitutes a case of convergent evolution in a subfamily of dasyurid
marsupials toward the cysteine-rich eutherian form of sperm protamine P1.
相似文献
87.
Rampant horizontal transfer and duplication of rubisco genes in eubacteria and plastids 总被引:16,自引:2,他引:14
Previous work has shown that molecular phylogenies of plastids,
cyanobacteria, and proteobacteria based on the rubisco (ribulose-1,5-
bisphosphate carboxylase/oxygenase) genes rbcL and rbcS are incongruent
with molecular phylogenies based on other genes and are also incompatible
with structural and biochemical information. Although it has been much
speculated that this is the consequence of a single horizontal gene
transfer (of a proteobacterial or mitochondrial rubisco operon into
plastids of rhodophytic and chromophytic algae), neither this hypothesis
nor the alternative hypothesis of ancient gene duplication have been
examined in detail. We have conducted phylogenetic analyses of all
available bacterial rbcL sequences, and representative plastid sequences,
in order to explore these alternative hypothesis and fully examine the
complexity of rubisco gene evolution. The rbcL phylogeny reveals a
surprising number of gene relationships that are fundamentally incongruent
with organismal relationships as inferred from multiple lines of other
molecular evidence. On the order of six horizontal gene transfers are
implied by the form I (L8S8) rbcL phylogeny, two between cyanobacteria and
proteobacteria, one between proteobacteria and plastids, and three within
proteobacteria. Alternatively, a single ancient duplication of the form I
rubisco operon, followed by repeated and pervasive differential loss of one
operon or the other, would account for much of this incongruity. In all
probability, the rubisco operon has undergone multiple events of both
horizontal gene transfer and gene duplication in different lineages.
相似文献
88.
Wodarz D Page KM Arnaout RA Thomsen AR Lifson JD Nowak MA 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2000,355(1395):329-343
We use simple mathematical models to examine the dynamics of primary and secondary cytotoxic T-lymphocyte (CTL) responses to viral infections. In particular, we are interested in conditions required to resolve the infection and to protect the host upon secondary challenge. While protection against reinfection is only effective in a restricted set of circumstances, we find that resolution of the primary infection requires persistence of CTL precursors (GTLp), as well as a fast rate of activation of the CTLp. Since these are commonly the defining characteristics of CTL memory, we propose that CTL memory may have evolved in order to clear the virus during primary challenge. We show experimental data from lymphocytic choriomeningitis virus infection in mice, supporting our theory on CTL memory. We adapt our models to HIV and find that immune impairment during the primary phase of the infection may result in the failure to establish CTL memory which in turn leads to viral persistence. Based on our models we suggest conceptual treatment regimes which ensure establishment of CTL memory. This would allow the immune response to control HIV in the long term in the absence of continued therapy. 相似文献
89.
CD4+ T-Lymphocyte Depletion in Human Lymphoid Tissue Ex Vivo Is Not Induced by Noninfectious Human Immunodeficiency Virus Type 1 Virions 下载免费PDF全文
A. W. Sylwester J.-C. Grivel W. Fitzgerald J. L. Rossio J. D. Lifson L. B. Margolis 《Journal of virology》1998,72(11):9345-9347
We tested infectious human immunodeficiency virus type 1 (HIV-1), noninfectious but conformationally authentic inactivated whole HIV-1 virions, and purified gp120 for the ability to induce depletion of CD4+ T cells in human lymphoid tissues ex vivo. Infectious CXCR4-tropic HIV-1, but not matched inactivated virions or gp120, mediated CD4+ T-cell depletion, consistent with mechanisms requiring productive infection. 相似文献
90.
The minimum energy conformations are calculated for 2, 5-diketopiperazine (DKP) and its 3,6-dimethyl derivatives (DL-DMDKP and LL-DMDKP), using a consistent force field approach developed previously. The energy function parameters that were not required in earlier calculations on alkanes, amides, mid lactams are fitted to spectral and conformational data on the diketopiperazines. Vibrational assignments are suggested for DKP. Conformational energies are also determined over a range of selected values for ring dihedral angles, and the shape of the potential energy functions is examined over deviations from planarity. DKP and LL-DMDKP are found to have non-planar minimum energy conformations, separated from planar by less than a kcal/mole. DL-DMKP exhibits a nearly flat trough about the planar conformation. Calculations of minimum energies with one dihedral angle coordinate constrainted show a coupling between bond angles and dihedral angles in agreement with recent suggestions of Benedetti. 相似文献