Molecular characterization of the HIV-1 gagnucleocapsid gene associated with vertical transmission

Wellensiek, Brian P.; Sundaravaradan, Vasudha; Ramakrishnan, Rajesh; Ahmad, Nafees

doi:10.1186/1742-4690-3-21

Cited by 13 publications

(3 citation statements)

References 65 publications

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“…Gag has been shown to have little antiviral function [39], however, it appears to be a strong target for antigen-specific immunoglobulin responses. The majority of immunoglobulins bind around the conserved NC, p8, and p6 regions of the Gag protein, which have several important functions in viral pathogenesis, such as viral replication, encapsulating the viral genome, aiding in reverse transcription, viral genome packaging, and viral budding [40]. While Gag is not a target for bNAbs, B-cell recognition of these highly important and conserved regions of the Gag protein may be indicative of a potential target for vaccine design.…”

Section: Discussionmentioning

confidence: 99%

Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques

Pahar

Kenway-Lynch

Marx

et al. 2016

Virol J

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BackgroundIncreasing evidence suggests an unexpected potential for non-neutralizing antibodies to prevent HIV infection. Consequently, identification of functional linear B-cell epitopes for HIV are important for developing preventative and therapeutic strategies. We therefore explored the role of antigen-specific immune responses in controlling plasma viremia in SIV infected rhesus macaques.MethodsThirteen rhesus macaques were inoculated either intravaginally or intrarectally with SIVMAC251. Peripheral blood CD4+ T-cells were quantified. Plasma was examined for viremia, antigen specific IgG, IgA and IgM binding responses and neutralizing antibodies. Regions containing binding epitopes for antigen-specific IgG, IgM and IgA responses were determined, and the minimum size of linear Envelope epitope responsible for binding antibodies was identified.ResultsThe presence of neutralizing antibodies did not correlate the outcome of the disease. In a few SIV-infected macaques, antigen-specific IgG and IgM responses in plasma correlated with decreased plasma viremia. Early induction and the breadth of antigen-specific IgG responses were found to be significantly correlated with the control of plasma viral load. Immunoglobulin classes share similar functional linear B-cell epitopes. SIV-specific linear envelope B-cell epitopes were found to be 12 amino-acids in length.ConclusionsEarly induction of combination of peptide-specific IgG responses were found to be responsible for the control of plasma viral load and indicative of disease outcome in SIV-infected rhesus macaques and might be important for the development of therapeutic strategies for control or prevention of HIV/AIDS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0652-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques

Pahar

Kenway-Lynch

Marx

et al. 2016

Virol J

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“…In a more comprehensive approach to understand the molecular properties of HIV-1 that are associated with vertical transmission, we showed that there was a high degree of preservation of the functional domains of HIV-1 in the structural genes, including gag p17 [ 24 ] and NC [ 25 ], pol RT [ 26 ], env gp120 [ 13 ] and gp41 [ 27 ], regulatory genes tat [ 28 ] and rev [ 29 ] and their cis-acting responsive regions, HIV-1 LTR [ 30 , 31 ] and RRE [ 32 ] and accessory genes, vif [ 33 ], vpr [ 34 ], vpu [ 35 ] and nef [ 36 ] from mother-infant pairs after vertical transmission. While most of these studies focused on elucidating the properties of HIV-1 associated with vertical transmission, limited studies have characterized the properties of HIV-1 that are associated with lack of vertical transmission.…”

Section: Characterization Of Viral Determinants Associated With Vertimentioning

confidence: 99%

Features of Maternal HIV-1 Associated with Lack of Vertical Transmission

Ahmad

2017

TOVJ

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HIV-1 is transmitted from mother-to-child (vertical transmission) at an estimated rate of approximately 30% without any antiretroviral therapy (ART). However, administration of ART during pregnancy considerably diminishes the rate of mother-to-child transmission of HIV-1, which has become a standard of perinatal care in HIV-infected pregnant females in developed countries. Moreover, a majority of children born to HIV-infected mothers are uninfected without any ART. In addition, characteristics of HIV-1 and/or cellular factors in the mothers may play a role in influencing or preventing vertical transmission. Several studies, including from our laboratory have characterized the properties of HIV-1 from infected mothers that transmitted HIV-1 to their infants (transmitting mothers) and compared with those mothers that failed to transmit HIV-1 to their infants (non-transmitting mothers) in the absence of ART. One of the striking differences observed was that the non-transmitting mothers harbored a less heterogeneous HIV-1 population than transmitting mothers in the analyzed HIV-1 regions of p17 gag, env V3, vif and vpr. The other significant and distinctive findings were that the functional domains of HIV-1 vif and vpr proteins were less conserved in non-transmitting mothers compared with transmitting mothers. Furthermore, there were differences seen in two important motifs of HIV-1 Gag p17, including conservation of QVSQNY motif and variation in KIEEEQN motif in non-transmitting mothers compared with transmitting mothers. Several of these distinguishing properties of HIV-1 in non-transmitting mothers provide insights in developing strategies for preventing HIV-1 vertical transmission.

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“…[31][32][33][34] It contains two well conserved zinc finger motifs (C-X2-C-X4-H-X4-C, CCHC) as the major functional domain required for the most of the above processes. [31][32][33][35][36][37] Mutations of CCHC motifs lead to a complete loss of these functions in addition to viral infectivity. 31,38,39 To induce effective major histocompatibility complex (MHC) class-I restricted cellular immune responses, antigens need to be effectively expressed endogenously.…”

Section: Construction and In Vitro Expression Of Gag Dna Vaccinesmentioning

confidence: 99%

Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1)

Wallace

West

Rothman

et al. 2013

Human Vaccines & Immunotherapeutics

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In the current study, immune responses induced by Gag DNA vaccines with different designs were evaluated in Balb/C mice. The results demonstrated that the DNA vaccine with the full length wild type gag gene (Wt-Gag) mainly produced Gag antigens intracellularly and induced a higher level of cell-mediated immune (CMI) responses, as measured by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and cytotoxic T lymphocytes (CTL) assays against a dominant CD8(+) T cell epitope (AMQMLKETI). In contrast, the addition of a tissue plasminogen activator (tPA) leader sequence significantly improved overall Gag protein expression/secretion and Gag-specific antibody responses; however, Gag-specific CMI responses were decreased. The mutation of zinc-finger motif changed Gag protein expression patterns and reduced the ability to generate both CMI and antibody responses against Gag. These findings indicate that the structure and post-translational processing of antigens expressed by DNA vaccines play a critical role in eliciting optimal antibody or CMI responses.

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Molecular characterization of the HIV-1 gagnucleocapsid gene associated with vertical transmission

Cited by 13 publications

References 65 publications

Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques

Breadth and magnitude of antigen-specific antibody responses in the control of plasma viremia in simian immunodeficiency virus infected macaques

Features of Maternal HIV-1 Associated with Lack of Vertical Transmission

Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1)

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