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  1. Article ; Online: Relative resistance of patient-derived envelope sequences to SERINC5-mediated restriction of HIV-1 infectivity.

    Nkuwi, Emmanuel / Judicate, George P / Tan, Toong Seng / Barabona, Godfrey / Toyoda, Mako / Sunguya, Bruno / Kamori, Doreen / Ueno, Takamasa

    Journal of virology

    2023  Volume 97, Issue 10, Page(s) e0082323

    Abstract: Importance: Pathogenesis of HIV-1 is enhanced through several viral-encoded proteins that counteract a range of host restriction molecules. HIV-1 Nef counteracts the cell membrane protein SERINC5 by downregulating it from the cell surface, thereby ... ...

    Abstract Importance: Pathogenesis of HIV-1 is enhanced through several viral-encoded proteins that counteract a range of host restriction molecules. HIV-1 Nef counteracts the cell membrane protein SERINC5 by downregulating it from the cell surface, thereby enhancing virion infectivity. Some subtype B reference Envelope sequences have shown the ability to bypass SERINC5 infectivity restriction independent of Nef. However, it is not clear if and to what extent circulating HIV-1 strains can exhibit resistance to SERINC5 restriction. Using a panel of Envelope sequences isolated from 50 Tanzanians infected with non-B HIV-1 subtypes, we show that the lentiviral reporters pseudotyped with patient-derived Envelopes have reduced sensitivity to SERINC5 and that this sensitivity differed among viral subtypes. Moreover, we found that SERINC5 sensitivity within patient-derived Envelopes can be modulated by separate regions, highlighting the complexity of viral/host interactions.
    MeSH term(s) Humans ; Cell Membrane/metabolism ; env Gene Products, Human Immunodeficiency Virus/genetics ; HIV Infections/metabolism ; HIV Infections/virology ; HIV-1/classification ; HIV-1/pathogenicity ; HIV-1/physiology ; Host Microbial Interactions ; Membrane Proteins/metabolism ; nef Gene Products, Human Immunodeficiency Virus/metabolism ; Tanzania
    Chemical Substances env Gene Products, Human Immunodeficiency Virus ; Membrane Proteins ; nef Gene Products, Human Immunodeficiency Virus ; SERINC5 protein, human
    Language English
    Publishing date 2023-09-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00823-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 609: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Advanced baseline immunosuppression is associated with elevated levels of plasma markers of fungal translocation and inflammation in long-term treated HIV-infected Tanzanians.

    Barabona, Godfrey / Mahiti, Macdonald / Toyoda, Mako / Kamori, Doreen / Masoud, Salim / Judicate, George P / Sunguya, Bruno / Lyamuya, Eligius / Ueno, Takamasa

    AIDS research and therapy

    2021  Volume 18, Issue 1, Page(s) 55

    Abstract: Background: For over a decade, antiretroviral therapy (ART) in resource-limited countries was only recommended for patients with advanced HIV disease. We investigated this group of patients in order to determine any relationship between degree of ... ...

    Abstract Background: For over a decade, antiretroviral therapy (ART) in resource-limited countries was only recommended for patients with advanced HIV disease. We investigated this group of patients in order to determine any relationship between degree of immunosuppression during treatment initiation and the subsequent levels of inflammatory biomarkers, reservoir size and plasma marker of fungal translocation after achieving long-term virological control.
    Methods: We analyzed 115 virally suppressed (female 83.5%) and 40 untreated (female 70%) subjects from Dar es Salaam, Tanzania. The size of HIV latent reservoir (proviral DNA copy) was determined using quantitative PCR. Inflammatory biomarkers; IL-6, IL-10, and soluble CD14 (sCD14), were measured using multiplex cytometric beads array. Antibody titers for Cytomegalovirus (CMV) and Epstein Barr virus (EBV), plasma level of 1-3-beta-D-Glucan (BDG) was measured using ELISA. High-sensitivity C-reactive protein (hsCRP) was measured using nephelometric method.
    Results: The median age was 36 (IQR 32-44) and 47 (IQR 43-54) years in untreated and virally suppressed patients respectively. Median duration of treatment for virally suppressed patients was 9 years (IQR 7-12) and median baseline CD4 count was 147 cells/mm
    Conclusions: Our data suggest that advanced immunosuppression at ART initiation is associated with severity of inflammation and elevated fungal translocation marker despite long term virological control. Further studies are needed to evaluate the potential increased burden of non-AIDS comorbidities that are linked to elevated inflammatory and fungal translocation markers as a result of the policy of HIV treatment at CD4 count < 200 cells/cm
    MeSH term(s) Adult ; Biomarkers ; Epstein-Barr Virus Infections ; Female ; HIV Infections/drug therapy ; Herpesvirus 4, Human ; Humans ; Immunosuppression Therapy ; Inflammation ; Tanzania
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-08-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2173450-1
    ISSN 1742-6405 ; 1742-6405
    ISSN (online) 1742-6405
    ISSN 1742-6405
    DOI 10.1186/s12981-021-00381-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Phenotypic and Genotypic Co-receptor Tropism Testing in HIV-1 Epidemic Region of Tanzania Where Multiple Non-B Subtypes Co-circulate.

    Judicate, George P / Barabona, Godfrey / Kamori, Doreen / Mahiti, Macdonald / Tan, Toong Seng / Ozono, Seiya / Mgunya, Amina Shaban / Kuwata, Takeo / Matsushita, Shuzo / Sunguya, Bruno / Lyamuya, Eligius / Tokunaga, Kenzo / Ueno, Takamasa

    Frontiers in microbiology

    2021  Volume 12, Page(s) 703041

    Abstract: HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly ... ...

    Abstract HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms remain insufficiently validated. To clarify this issue, we recruited 52 treatment-naïve, HIV-1-infected patients in Tanzania, where multiple HIV-1 non-B subtypes co-circulate. Sequence analysis of 93 infectious envelope clones isolated from their plasma viral RNA revealed the co-circulation of subtypes A1, C, D, and inter-subtype recombinant forms (isRFs). Phenotypic tropism assays revealed that lentivirus reporters pseudotyped with 75 (80.6%) and 5 (5.4%) envelope clones could establish infection toward U87.CD4 cells expressing CCR5 (R5) and CXCR4 (X4), respectively; whereas the remaining 13 (14%) clones could infect both cells. Genotypic analyses by widely used algorithms including V3 net charge, Geno2pheno, WebPSSM, and PhenoSeq showed that almost all phenotypic X4-tropic clones and only 15 of 75 phenotypic R5-tropic clones were concordantly predicted. However, the remaining 60 phenotypic R5-tropic clones were discordantly predicted by at least one algorithm. In particular, 2 phenotypic R5-tropic clones were discordantly predicted by all algorithms tested. Taken together, the results demonstrate the limitation of currently available genotypic algorithms for predicting co-receptor inference among co-circulating multiple non-B subtypes and emerging isRFs. Also, the phenotypic tropism dataset presented here could be valuable for retraining of the widely used genotypic prediction algorithms to enhance their performance.
    Language English
    Publishing date 2021-07-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.703041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterization of a Novel CD4 Mimetic Compound YIR-821 against HIV-1 Clinical Isolates.

    Matsumoto, Kaho / Kuwata, Takeo / Tolbert, William D / Richard, Jonathan / Ding, Shilei / Prévost, Jérémie / Takahama, Shokichi / Judicate, George P / Ueno, Takamasa / Nakata, Hirotomo / Kobayakawa, Takuya / Tsuji, Kohei / Tamamura, Hirokazu / Smith, Amos B / Pazgier, Marzena / Finzi, Andrés / Matsushita, Shuzo

    Journal of virology

    2022  Volume 97, Issue 1, Page(s) e0163822

    Abstract: Small CD4-mimetic compound (CD4mc), which inhibits the interaction between gp120 with CD4, acts as an entry inhibitor and induces structural changes in the HIV-1 envelope glycoprotein trimer (Env) through its insertion within the Phe43 cavity of gp120. ... ...

    Abstract Small CD4-mimetic compound (CD4mc), which inhibits the interaction between gp120 with CD4, acts as an entry inhibitor and induces structural changes in the HIV-1 envelope glycoprotein trimer (Env) through its insertion within the Phe43 cavity of gp120. We recently developed YIR-821, a novel CD4mc, that has potent antiviral activity and lower toxicity than the prototype NBD-556. To assess the possibility of clinical application of YIR-821, we tested its antiviral activity using a panel of HIV-1 pseudoviruses from different subtypes. YIR-821 displayed entry inhibitor activity against 53.5% (21/40) of the pseudoviruses tested and enhanced neutralization mediated by coreceptor binding site (CoRBS) antibodies in 50% (16/32) of these. Furthermore, when we assessed the antiviral effects using a panel of pseudoviruses and autologous plasma IgG, enhancement of antibody-mediated neutralization activity was observed for 48% (15/31) of subtype B strains and 51% (28/55) of non-B strains. The direct antiviral activity of YIR-821 as an entry inhibitor was observed in 53% of both subtype B (27/51) and non-B subtype (40/75) pseudoviruses. Enhancement of antibody-dependent cellular cytotoxicity was also observed with YIR-821 for all six selected clinical isolates, as well as for the transmitted/founder (T/F) CH58 virus-infected cells. The sequence diversity in the CD4 binding site as well as other regions, such as the gp120 inner domain layers or gp41, may be involved in the multiple mechanisms related to the sensitive/resistant phenotype of the virus to YIR-821. Our findings may facilitate the clinical application of YIR-821.
    MeSH term(s) Animals ; CD4 Antigens/metabolism ; HIV Antibodies/blood ; HIV Envelope Protein gp120 ; HIV Fusion Inhibitors/pharmacology ; HIV Infections/drug therapy ; HIV-1/drug effects ; Immunoglobulin G/blood ; Macaca mulatta
    Chemical Substances CD4 Antigens ; HIV Antibodies ; HIV Envelope Protein gp120 ; HIV Fusion Inhibitors ; Immunoglobulin G
    Language English
    Publishing date 2022-12-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.01638-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 609: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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