Buy The Role of the HIV-1 V3 Loop in Determining Coreceptor Tropism and Modulating Sensitivity to Coreceptor Inhibitors
close menu
Bookswagon
search
My Account
Book 1
Book 2
Book 3
Book 1
Book 2
Book 3
Book 1
Book 2
Book 3
Book 1
Book 2
Book 3
Home > Mathematics and Science Textbooks > Biology, life sciences > The Role of the HIV-1 V3 Loop in Determining Coreceptor Tropism and Modulating Sensitivity to Coreceptor Inhibitors
The Role of the HIV-1 V3 Loop in Determining Coreceptor Tropism and Modulating Sensitivity to Coreceptor Inhibitors

The Role of the HIV-1 V3 Loop in Determining Coreceptor Tropism and Modulating Sensitivity to Coreceptor Inhibitors


     0     
5
4
3
2
1



Out of Stock


Notify me when this book is in stock
X
About the Book

In order for an HIV-1 virion to infect a host cell, the gp120 subunit of envelope, the only viral protein exposed on the surface of the virion, first attaches to the cellular receptor CD4 and subsequently to a chemokine coreceptor, either CCR5 or CXCR4. Tropism for these coreceptors is principally determined by the V3 loop, which is a 35-residue region bound by a disulphide bond and exposed on the surface of gp120. While V3 is known to be critical for coreceptor binding, V3-coreceptor interactions and the structural basis for CCR5 or CXCR4 specificity remain elusive. We hypothesized that subdomains within V3 determine coreceptor tropism. Using the dual-tropic virus HIV-1R3A, which uses both CCR5 and CXCR4, we made an extensive panel of small V3 deletions and evaluated these mutants for their effects on tropism and sensitivity to coreceptor antagonists. Small deletions on either side of the V3 base abrogated R5 tropism. The resulting X4-tropic mutants exhibited enhanced sensitivity to the CXCR4 antagonist AMD3100. Only a deletion of residues 9 to 12 in the V3 stem ablated X4 tropism. Remarkably, this R5-tropic mutant showed complete resistance to a panel of CCR5 antagonists, including vicriviroc and aplaviroc. Our findings suggest that subdomains in V3 differentially affect R5 and X4 tropism and modulate sensitivity to coreceptor antagonists. Small molecule CCR5 inhibitors are being used clinically to treat HIV-1-infected patients, so in order to study mechanisms of resistance to this new drug class, we further characterized a variant of the drug-resistant Delta9-12 mutant, termed Delta9-12a. Since CCR5 antagonists disrupt the gp120-CCR5 extracellular loop interaction, we hypothesized that Delta9-12a is more dependent on the CCR5 amino terminus (NT). Our results indicate that Delta9-12a does have an increased reliance on the CCR5 NT, exhibits increased sensitivity to several broadly neutralizing monoclonal antibodies, including b12 and 4E10, and is capable of using aplaviroc-bound CCR5. This detailed characterization suggests that increased dependence on the CCR5 NT may represent a mechanism by which HIV-1 Envs acquire resistance to CCR5 antagonists. In addition, envelopes such as Delta9-12a may be useful for identifying new drugs that target the gpl20-CCR5 NT interaction.


Best Sellers


Product Details
  • ISBN-13: 9781243542731
  • Publisher: Proquest, Umi Dissertation Publishing
  • Publisher Imprint: Proquest, Umi Dissertation Publishing
  • Height: 246 mm
  • Weight: 299 gr
  • ISBN-10: 124354273X
  • Publisher Date: 01 Sep 2011
  • Binding: Paperback
  • Spine Width: 9 mm
  • Width: 189 mm


Similar Products

Add Photo
Add Photo

Customer Reviews

REVIEWS      0     
Click Here To Be The First to Review this Product
The Role of the HIV-1 V3 Loop in Determining Coreceptor Tropism and Modulating Sensitivity to Coreceptor Inhibitors
Proquest, Umi Dissertation Publishing -
The Role of the HIV-1 V3 Loop in Determining Coreceptor Tropism and Modulating Sensitivity to Coreceptor Inhibitors
Writing guidlines
We want to publish your review, so please:
  • keep your review on the product. Review's that defame author's character will be rejected.
  • Keep your review focused on the product.
  • Avoid writing about customer service. contact us instead if you have issue requiring immediate attention.
  • Refrain from mentioning competitors or the specific price you paid for the product.
  • Do not include any personally identifiable information, such as full names.

The Role of the HIV-1 V3 Loop in Determining Coreceptor Tropism and Modulating Sensitivity to Coreceptor Inhibitors

Required fields are marked with *

Review Title*
Review
    Add Photo Add up to 6 photos
    Would you recommend this product to a friend?
    Tag this Book Read more
    Does your review contain spoilers?
    What type of reader best describes you?
    I agree to the terms & conditions
    You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.

    CUSTOMER RATINGS AND REVIEWS AND QUESTIONS AND ANSWERS TERMS OF USE

    These Terms of Use govern your conduct associated with the Customer Ratings and Reviews and/or Questions and Answers service offered by Bookswagon (the "CRR Service").


    By submitting any content to Bookswagon, you guarantee that:
    • You are the sole author and owner of the intellectual property rights in the content;
    • All "moral rights" that you may have in such content have been voluntarily waived by you;
    • All content that you post is accurate;
    • You are at least 13 years old;
    • Use of the content you supply does not violate these Terms of Use and will not cause injury to any person or entity.
    You further agree that you may not submit any content:
    • That is known by you to be false, inaccurate or misleading;
    • That infringes any third party's copyright, patent, trademark, trade secret or other proprietary rights or rights of publicity or privacy;
    • That violates any law, statute, ordinance or regulation (including, but not limited to, those governing, consumer protection, unfair competition, anti-discrimination or false advertising);
    • That is, or may reasonably be considered to be, defamatory, libelous, hateful, racially or religiously biased or offensive, unlawfully threatening or unlawfully harassing to any individual, partnership or corporation;
    • For which you were compensated or granted any consideration by any unapproved third party;
    • That includes any information that references other websites, addresses, email addresses, contact information or phone numbers;
    • That contains any computer viruses, worms or other potentially damaging computer programs or files.
    You agree to indemnify and hold Bookswagon (and its officers, directors, agents, subsidiaries, joint ventures, employees and third-party service providers, including but not limited to Bazaarvoice, Inc.), harmless from all claims, demands, and damages (actual and consequential) of every kind and nature, known and unknown including reasonable attorneys' fees, arising out of a breach of your representations and warranties set forth above, or your violation of any law or the rights of a third party.


    For any content that you submit, you grant Bookswagon a perpetual, irrevocable, royalty-free, transferable right and license to use, copy, modify, delete in its entirety, adapt, publish, translate, create derivative works from and/or sell, transfer, and/or distribute such content and/or incorporate such content into any form, medium or technology throughout the world without compensation to you. Additionally,  Bookswagon may transfer or share any personal information that you submit with its third-party service providers, including but not limited to Bazaarvoice, Inc. in accordance with  Privacy Policy


    All content that you submit may be used at Bookswagon's sole discretion. Bookswagon reserves the right to change, condense, withhold publication, remove or delete any content on Bookswagon's website that Bookswagon deems, in its sole discretion, to violate the content guidelines or any other provision of these Terms of Use.  Bookswagon does not guarantee that you will have any recourse through Bookswagon to edit or delete any content you have submitted. Ratings and written comments are generally posted within two to four business days. However, Bookswagon reserves the right to remove or to refuse to post any submission to the extent authorized by law. You acknowledge that you, not Bookswagon, are responsible for the contents of your submission. None of the content that you submit shall be subject to any obligation of confidence on the part of Bookswagon, its agents, subsidiaries, affiliates, partners or third party service providers (including but not limited to Bazaarvoice, Inc.)and their respective directors, officers and employees.

    Accept


    Inspired by your browsing history


    Your review has been submitted!

    You've already reviewed this product!