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About: Neutralization is a(n) research topic. Over the lifetime, 3158 publication(s) have been published within this topic receiving 119880 citation(s). more


Open accessJournal ArticleDOI: 10.1016/S0021-9258(19)67936-6
Bruce N. Ames1, Donald T. Dubin1Institutions (1)
Abstract: It was previously reported that bacteriophage T4 contains the polyamines putrescine, NH2(CH2)$;IH2, and spermidine, NHQ(CH&NH(CH&NH2, in amounts sufficient to neutralize about half of the viral deoxyribonucleic acid (1). The putrescine and spermidine in the phage were found to be derived from the large amount of these polyamines normally present in the host bacterium, Escherichia coli B. It was also shown that these cations are the unidentified compounds in phage T2 reported by Hershey to be injected into the bacteria along with the viral DNA (2). In the present communication we have attempted to answer certain questions raised by these findings: 1. Is the role of the polyamines in phage that of specific or nonspecific cations for neutralizing the negatively charged phosphate groups in the DNA? 2. Are the amounts and kinds of polyamines in the phage determined by the phage or by the bacterial pool of cations? 3. Can stoichiometry between cations in the phage and the phosphate anions of the DNA be demonstrated? 4. What is the distribution of polyamines in viruses? The cations of T4 phage have been examined and a balance has been obtained between total cations and total DNA anions. The normal cation content of T4 (putrescine++, spermiclme+++, and Mg++) was changed markedly under certain conditions. When the host bacterium E. coli B was grown on minimal medium contaming spermine, NH2(CH2)3NH(CH&NH(CH&NH~, a polyamine present in animal tissues (3, 4) but not generally present in bacteria (5), the putrescine and spermidine normally present in the E. coli were replaced by spermine and acetylated spermine (6). These abnormal polyamines were found as the main polyamines in the T4 phage grown on these bacteria. The replacement of the normal polyamines suggested that the polyamines may be acting as nonspecific cations. Two types of evidence support this hypothesis. The lack of polyamines in various bacteriophages (T3, T5, P22) has been correlated with the permeability of these phages to cations; it seems as if the polyamines were displaced by other cations during the purification of the phage. When Brenner’s (7) permeable (osmotic-shock resistant) mutant of T4 was washed with Mg++, a preparation of phage was obtained containing essentially no polyamines; when the mutant phage was washed with spermidine and then with water, a balance was obtained between the DNA anions and the spermidine cations. The properties of preparations of T4 phage containing various cations have been examined. more

Topics: Neutralization (54%)

2,460 Citations

Open accessJournal ArticleDOI: 10.1126/SCIENCE.1187659
Xueling Wu1, Zhi Yong Yang1, Yuxing Li1, Carl Magnus Hogerkorp1  +20 moreInstitutions (3)
13 Aug 2010-Science
Abstract: Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design. more

Topics: Neutralizing antibody (56%), Monoclonal antibody (54%), Viral envelope (52%) more

1,582 Citations

Journal ArticleDOI: 10.1126/SCIENCE.7973652
11 Nov 1994-Science
Abstract: The ability of antibodies to neutralize diverse primary isolates of human immunodeficiency virus-type 1 in vitro has been questioned, with implications for the likely efficacy of vaccines. A recombinant human antibody to envelope glycoprotein gp120 was generated and used to show that primary isolates are not refractory to antibody neutralization. The recombinant antibody neutralized more than 75 percent of the primary isolates tested at concentrations that could be achieved by passive immunization, for example, to interrupt maternal-fetal transmission of virus. The broad specificity and efficacy of the antibody implies the conservation of a structural feature on gp120, which could be important in vaccine design. more

Topics: Neutralization (53%), Antibody (52%), Monoclonal antibody (52%) more

1,196 Citations

Open accessJournal ArticleDOI: 10.1126/SCIENCE.1192819
Tongqing Zhou1, Ivelin S. Georgiev1, Xueling Wu1, Zhi Yong Yang1  +15 moreInstitutions (4)
13 Aug 2010-Science
Abstract: During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies. more

Topics: Affinity maturation (55%), Neutralization (54%), Viral envelope (53%) more

1,056 Citations

Open accessJournal ArticleDOI: 10.1128/JVI.55.3.836-839.1985
Abstract: Comparative surface feature analyses of the VP1 sequences of hepatitis A virus (HAV) and poliovirus type 1 allowed an alignment of the two sequences and an identification of probable HAV neutralization antigenic sites. A synthetic peptide containing the HAV-specific amino acid sequence of one of these sites induced anti-HAV-neutralizing antibodies. It is concluded that a structural homology exists between the two viruses, despite minimal primary sequence conservation. more

Topics: Peptide sequence (57%), Neutralizing antibody (56%), Virus (55%) more

1,045 Citations

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Topic's top 5 most impactful authors

David C. Montefiori

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Dennis R. Burton

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John R. Mascola

33 papers, 5.9K citations

Susan Zolla-Pazner

30 papers, 2.2K citations

Michael S. Seaman

17 papers, 2.6K citations

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