NDLI: Net Positive Charge of HIV-1 CRF01_AE V3 Sequence Regulates Viral Sensitivity to Humoral Immunity

Content Provider	PubMed Central
Author	Naganawa, Satoshi Yokoyama, Masaru Shiino, Teiichiro Suzuki, Takeyuki Yoshiaki, Ishigatsubo Ueda, Atsuhisa Shirai, Akira Takeno, Mitsuhiro Hayakawa, Satoshi Sato, Shigehiro Tochikubo, Osamu Kiyoura, Shingo Sawada, Kaori Ikegami, Takashi Kanda, Tadahito Kitamura, Katsuhiko Sato, Hironori
Editor	Zhang, Linqi
Copyright Year	2008
Abstract	The third variable region (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope gp120 subunit participates in determination of viral infection coreceptor tropism and host humoral immune responses. Positive charge of the V3 plays a key role in determining viral coreceptor tropism. Here, we examined by bioinformatics, experimental, and protein modelling approaches whether the net positive charge of V3 sequence regulates viral sensitivity to humoral immunity. We chose HIV-1 CRF01_AE strain as a model virus to address the question. Diversity analyses using CRF01_AE V3 sequences from 37 countries during 1984 and 2005 (n = 1361) revealed that reduction in the V3's net positive charge makes V3 less variable due to limited positive selection. Consistently, neutralization assay using CRF01_AE V3 recombinant viruses (n = 30) showed that the reduction in the V3's net positive charge rendered HIV-1 less sensitive to neutralization by the blood anti-V3 antibodies. The especially neutralization resistant V3 sequences were the particular subset of the CCR5-tropic V3 sequences with net positive charges of +2 to +4. Molecular dynamics simulation of the gp120 monomers showed that the V3's net positive charge regulates the V3 configuration. This and reported gp120 structural data predict a less-exposed V3 with a reduced net positive charge in the native gp120 trimer context. Taken together, these data suggest a key role of the V3's net positive charge in the immunological escape and coreceptor tropism evolution of HIV-1 CRF01_AE in vivo. The findings have molecular implications for the adaptive evolution and vaccine design of HIV-1.
Related Links	http://dx.doi.org/10.1371/journal.pone.0003206
Starting Page	3206
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	9
Volume Number	3
Language	English
Publisher	Public Library of Science
Publisher Date	2008-09-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Molecular Evolution of HIV-1 CRF01_AE Env in Thai Patients

Effect of Lysine to Arginine Mutagenesis in the V3 Loop of HIV-1 gp120 on Viral Entry Efficiency and Neutralization

Susceptibility of HIV-1 Subtypes B′, CRF07_BC and CRF01_AE that Are Predominantly Circulating in China to HIV-1 Entry Inhibitors

Correction: Hybrid Approach for Predicting Coreceptor Used by HIV-1 from Its V3 Loop Amino Acid Sequence

Identification of a Novel HIV-1 Intra-CRF01_AE in China: A Descendant of the Previously Identified CRF01_AE transmission clusters 1 and 6

B Cell Depletion in HIV-1 Subtype A Infected Ugandan Adults: Relationship to CD4 T Cell Count, Viral Load and Humoral Immune Responses

Unique CRF01_AE Gag CTL Epitopes Associated with Lower HIV-Viral Load and Delayed Disease Progression in a Cohort of HIV-Infected Thais

V3-Independent Competitive Resistance of a Dual-X4 HIV-1 to the CXCR4 Inhibitor AMD3100

Multiple Independent Introductions of HIV-1 CRF01_AE Identified in China: What Are the Implications for Prevention?

Net Positive Charge of HIV-1 CRF01_AE V3 Sequence Regulates Viral Sensitivity to Humoral Immunity

Similar Documents

Molecular Evolution of HIV-1 CRF01_AE Env in Thai Patients

Effect of Lysine to Arginine Mutagenesis in the V3 Loop of HIV-1 gp120 on Viral Entry Efficiency and Neutralization

Susceptibility of HIV-1 Subtypes B′, CRF07_BC and CRF01_AE that Are Predominantly Circulating in China to HIV-1 Entry Inhibitors

Correction: Hybrid Approach for Predicting Coreceptor Used by HIV-1 from Its V3 Loop Amino Acid Sequence

Identification of a Novel HIV-1 Intra-CRF01_AE in China: A Descendant of the Previously Identified CRF01_AE transmission clusters 1 and 6

B Cell Depletion in HIV-1 Subtype A Infected Ugandan Adults: Relationship to CD4 T Cell Count, Viral Load and Humoral Immune Responses

Unique CRF01_AE Gag CTL Epitopes Associated with Lower HIV-Viral Load and Delayed Disease Progression in a Cohort of HIV-Infected Thais

V3-Independent Competitive Resistance of a Dual-X4 HIV-1 to the CXCR4 Inhibitor AMD3100

Multiple Independent Introductions of HIV-1 CRF01_AE Identified in China: What Are the Implications for Prevention?

Net Positive Charge of HIV-1 CRF01_AE V3 Sequence Regulates Viral Sensitivity to Humoral Immunity