JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
The variable loop 3 in the envelope glycoprotein is critical for the atypical coreceptor usage of an HIV-1 strain.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The majority of HIV-1 strains enter CD4+ T cells using the CCR5 and/or CXCR4 co-receptor. However, we recently identified a transmitted/founder (T/F) virus (ZP6248) that efficiently used an alternative coreceptor GPR15, rather than commonly used CXCR4 and CCR5, to establish clinical infection. To understand which regions in the env gene were critical for the atypical coreceptor usage, we generated a set of V3 mutants and determined their infectivity in GHOST cells that expressed different coreceptors. When the variable loop 3 (V3) in YU2 was replaced with the ZP6248 V3 (YU2.6248V3), the chimera YU2.6248V3 infected GPR15+ cells but not CCR5+ cells. To determine which amino acids in V3 was responsible for this phenotype change, each of the eight amino acids that differed from the subtype B consensus V3 was substituted with alanine. The G306A and S322A mutations significantly reduced the replication capacity of YU2.6248V3 in GPR15+ cells, while all other alanine substitutions at positions 307, 314, 315, 316, 317 and 318 completely abrogated the infectivity of YU2.6248V3 in GPR15+ cells. The E314A mutation, as the E314G mutation reported before, also rendered the YU2.6248V3 infectious in CCR5+ cells, while none of other alanine mutants could infect CCR5+ cells. These results demonstrated that amino acids in ZP6248 V3 might form a unique conformation that was critical for the interaction with GPR15 while the amino acids at position 314 in the V3 crown of ZP6248 played a key role in interaction with both CCR5 and GPR15. The unique phenotypes of ZP6248 can serve as a model to understand how HIV-1 explores the diverse coreceptor reservoir through novel genetic variants to establish clinical infection.
Related JoVE Video
Antitumor effect of adenoviral vector prime protein boost immunity targeting the MUC1 VNTRs.
Oncol. Rep.
PUBLISHED: 10-17-2013
Show Abstract
Hide Abstract
Mucin 1 (MUC1) is a tumor-associated antigen that is overexpressed in several adenocarcinomas. However, clinical trials with MUC1 showed that MUC1 is a relatively poor immunogen in humans. In view of the low immunogenicity of this protein vaccine, we designed a method based on an immunoadjuvant and immunization strategy to enhance the cellular immune response to this protein vaccine. DDA/MPL has been evaluated as an adjuvant to induce strong immunity for the tuberculosis vaccine. However, its adjuvant role combined with the vaccine targeting MUC1 in malignant carcinomas has not previously been reported. Our previous study showed that adenovirus prime protein boost vaccination could significantly enhance the cellular immunity and antitumor efficacy. In our study, we used MUC1 VNTRs as the target of cancer vaccine and DDA/MPL as the adjuvant to enhancing the cellular immunity of recombinant MUC1 protein vaccine, and an AD-9M adenoviral vector prime-recombinant protein and DDA/MPL boost (designated MUC-1 VPP vaccine) strategy was studied to enhance the antitumor efficacy. The results demonstrated that antigen-specific IFN-?-secreting T cells were increased by 2-fold, and cytotoxic T lymphocytes (CTLs) were induced effectively when the protein vaccine was combined with the DDA/MPL adjuvant. Moreover, the vaccination induced nearly 60% inhibition of the growth of B16 melanoma in mice and prolonged the survival of tumor-bearing mice. The inhibition was correlated with the specific immune responses induced by the MUC1 VPP vaccine. The data suggested that DDA/MPL-adjuvant MUC-1 VPP vaccine may be developed into effective tumor vaccines for melanomas and possibly for other tumors expressing MUC1 protein.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.