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  1. Article ; Online: HIV establishes an early foothold.

    Moran, Jose A / Marsden, Matthew D

    Cell host & microbe

    2023  Volume 31, Issue 4, Page(s) 571–573

    Abstract: The weeks following HIV acquisition are a critical time when the virus causes significant immunological damage and establishes long-term latent reservoirs. A recent study in Immunity by Gantner et al. uses single-cell analysis to explore these key early ... ...

    Abstract The weeks following HIV acquisition are a critical time when the virus causes significant immunological damage and establishes long-term latent reservoirs. A recent study in Immunity by Gantner et al. uses single-cell analysis to explore these key early infection events, providing insights into early HIV pathogenesis and reservoir formation.
    MeSH term(s) Humans ; HIV Infections ; Virus Latency ; CD4-Positive T-Lymphocytes
    Language English
    Publishing date 2023-04-13
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2023.03.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Benefits and limitations of humanized mice in HIV persistence studies.

    Marsden, Matthew D

    Retrovirology

    2020  Volume 17, Issue 1, Page(s) 7

    Abstract: Significant advances in the treatment of HIV infection have been made in the last three decades. Antiretroviral therapy (ART) is now potent enough to prevent virus replication and stop disease progression. However, ART alone does not cure the infection, ... ...

    Abstract Significant advances in the treatment of HIV infection have been made in the last three decades. Antiretroviral therapy (ART) is now potent enough to prevent virus replication and stop disease progression. However, ART alone does not cure the infection, primarily because HIV can persist in stable long-term reservoir cells including latently-infected CD4 + T cells. A central goal of the HIV research field is to devise strategies to eliminate these reservoirs and thereby develop a cure for HIV. This requires robust in vivo model systems to facilitate both the further characterization of persistent HIV reservoirs and evaluation of methods for eliminating latent virus. Humanized mice have proven to be versatile experimental models for studying many basic aspects of HIV biology. These models consist of immunodeficient mice transplanted with human cells or tissues, which allows development of a human immune system that supports robust infection with HIV. There are many potential applications for new generations of humanized mouse models in investigating HIV reservoirs and latency, but these models also involve caveats that are important to consider in experimental design and interpretation. This review briefly discusses some of the key strengths and limitations of humanized mouse models in HIV persistence studies.
    MeSH term(s) Animals ; Disease Models, Animal ; HIV Infections/virology ; HIV-1/immunology ; Humans ; Mice ; Mice, Transgenic ; Viral Load ; Virus Latency ; Virus Replication
    Language English
    Publishing date 2020-04-06
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 1742-4690
    ISSN (online) 1742-4690
    DOI 10.1186/s12977-020-00516-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Can macrophages form a latent reservoir of HIV?

    Pham, Victor / Marsden, Matthew D

    Future virology

    2021  Volume 16, Issue 2, Page(s) 75–77

    Language English
    Publishing date 2021-01-20
    Publishing country England
    Document type Editorial
    ZDB-ID 2254606-6
    ISSN 1746-0808 ; 1746-0794
    ISSN (online) 1746-0808
    ISSN 1746-0794
    DOI 10.2217/fvl-2020-0381
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  4. Article ; Online: Contribution of Sex Differences to HIV Immunology, Pathogenesis, and Cure Approaches.

    Moran, Jose A / Turner, Shireen R / Marsden, Matthew D

    Frontiers in immunology

    2022  Volume 13, Page(s) 905773

    Abstract: Approximately 38 million people were living with human immunodeficiency virus (HIV) in 2020 and 53% of those infected were female. A variety of virological and immunological sex-associated differences (sexual dimorphism) in HIV infection have been ... ...

    Abstract Approximately 38 million people were living with human immunodeficiency virus (HIV) in 2020 and 53% of those infected were female. A variety of virological and immunological sex-associated differences (sexual dimorphism) in HIV infection have been recognized in males versus females. Social, behavioral, and societal influences play an important role in how the HIV pandemic has affected men and women differently. However, biological factors including anatomical, physiologic, hormonal, and genetic differences in sex chromosomes can each contribute to the distinct characteristics of HIV infection observed in males versus females. One striking example of this is the tendency for women to have lower HIV plasma viral loads than their male counterparts early in infection, though both progress to AIDS at similar rates. Sex differences in acquisition of HIV, innate and adaptive anti-HIV immune responses, efficacy/suitability of specific antiretroviral drugs, and viral pathogenesis have all been identified. Sex differences also have the potential to affect viral persistence, latency, and cure approaches. In this brief review, we summarize the major biological male/female sex differences in HIV infection and their importance to viral acquisition, pathogenesis, treatment, and cure efforts.
    MeSH term(s) Anti-Retroviral Agents/therapeutic use ; Female ; HIV Infections ; Humans ; Male ; Sex Characteristics
    Chemical Substances Anti-Retroviral Agents
    Language English
    Publishing date 2022-05-25
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.905773
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  5. Article: Experimental Approaches for Eliminating Latent HIV.

    Marsden, Matthew D / Zack, Jerome A

    Forum on immunopathological diseases and therapeutics

    2017  Volume 6, Issue 1-2, Page(s) 91–99

    Abstract: Antiretroviral therapy (ART) can reduce HIV viral loads to undetectable levels and prevent disease progression. However, HIV persists in rare cellular reservoirs within ART-treated patients and rapidly reemerges if ART is stopped. Latently infected ... ...

    Abstract Antiretroviral therapy (ART) can reduce HIV viral loads to undetectable levels and prevent disease progression. However, HIV persists in rare cellular reservoirs within ART-treated patients and rapidly reemerges if ART is stopped. Latently infected CD4
    Language English
    Publishing date 2017-01-16
    Publishing country United States
    Document type Journal Article
    ISSN 2151-8017
    ISSN 2151-8017
    DOI 10.1615/forumimmundisther.2016015242
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  6. Article ; Online: Secreted factors induced by PKC modulators do not indirectly cause HIV latency reversal.

    Moran, Jose A / Ranjan, Alok / Hourani, Rami / Kim, Jocelyn T / Wender, Paul A / Zack, Jerome A / Marsden, Matthew D

    Virology

    2023  Volume 581, Page(s) 8–14

    Abstract: HIV can establish a long-lived latent infection in cells harboring integrated non-expressing proviruses. Latency reversing agents (LRAs), including protein kinase C (PKC) modulators, can induce expression of latent HIV, thereby reducing the latent ... ...

    Abstract HIV can establish a long-lived latent infection in cells harboring integrated non-expressing proviruses. Latency reversing agents (LRAs), including protein kinase C (PKC) modulators, can induce expression of latent HIV, thereby reducing the latent reservoir in animal models. However, PKC modulators such as bryostatin-1 also cause cytokine upregulation in peripheral blood mononuclear cells (PBMCs), including cytokines that might independently reverse HIV latency. To determine whether cytokines induced by PKC modulators contribute to latency reversal, primary human PBMCs were treated with bryostatin-1 or the bryostatin analog SUW133, a superior LRA, and supernatant was collected. As anticipated, LRA-treated cell supernatant contained increased levels of cytokines compared to untreated cell supernatant. However, exposure of latently-infected cells with this supernatant did not result in latency reactivation. These results indicate that PKC modulators do not have significant indirect effects on HIV latency reversal in vitro and thus are targeted in their latency reversing ability.
    MeSH term(s) Animals ; Humans ; Virus Latency ; HIV Infections ; Bryostatins/pharmacology ; Leukocytes, Mononuclear ; CD4-Positive T-Lymphocytes ; HIV-1/physiology ; Cytokines/metabolism ; Virus Activation
    Chemical Substances bryostatin 1 (37O2X55Y9E) ; Bryostatins ; Cytokines
    Language English
    Publishing date 2023-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2023.02.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Humanized Mouse Models for Human Immunodeficiency Virus Infection.

    Marsden, Matthew D / Zack, Jerome A

    Annual review of virology

    2017  Volume 4, Issue 1, Page(s) 393–412

    Abstract: Human immunodeficiency virus (HIV) remains a significant source of morbidity and mortality worldwide. No effective vaccine is available to prevent HIV transmission, and although antiretroviral therapy can prevent disease progression, it does not cure HIV ...

    Abstract Human immunodeficiency virus (HIV) remains a significant source of morbidity and mortality worldwide. No effective vaccine is available to prevent HIV transmission, and although antiretroviral therapy can prevent disease progression, it does not cure HIV infection. Substantial effort is therefore currently directed toward basic research on HIV pathogenesis and persistence and developing methods to stop the spread of the HIV epidemic and cure those individuals already infected with HIV. Humanized mice are versatile tools for the study of HIV and its interaction with the human immune system. These models generally consist of immunodeficient mice transplanted with human cells or reconstituted with a near-complete human immune system. Here, we describe the major humanized mouse models currently in use, and some recent advances that have been made in HIV research/therapeutics using these models.
    MeSH term(s) Acquired Immunodeficiency Syndrome/immunology ; Acquired Immunodeficiency Syndrome/virology ; Animals ; Anti-HIV Agents/therapeutic use ; Disease Models, Animal ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/immunology ; HIV-1/physiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunologic Deficiency Syndromes ; Leukocyte Transfusion ; Mice ; Mice, SCID
    Chemical Substances Anti-HIV Agents
    Language English
    Publishing date 2017-07-26
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2764224-0
    ISSN 2327-0578 ; 2327-056X
    ISSN (online) 2327-0578
    ISSN 2327-056X
    DOI 10.1146/annurev-virology-101416-041703
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  8. Article ; Online: Double trouble: HIV latency and CTL escape.

    Marsden, Matthew D / Zack, Jerome A

    Cell host & microbe

    2015  Volume 17, Issue 2, Page(s) 141–142

    Abstract: HIV can enter a state of latency that allows it to persist for decades in antiretroviral drug-treated patients. In a recent Nature paper, Deng et al. (2015) show that this latent reservoir also contains a large number of cytotoxic T lymphocyte escape ... ...

    Abstract HIV can enter a state of latency that allows it to persist for decades in antiretroviral drug-treated patients. In a recent Nature paper, Deng et al. (2015) show that this latent reservoir also contains a large number of cytotoxic T lymphocyte escape mutants, presenting another challenge to HIV cure efforts.
    MeSH term(s) Animals ; Female ; Genes, Dominant/genetics ; Genes, Viral/genetics ; HIV-1/genetics ; HIV-1/immunology ; Humans ; Male ; Mutation/genetics ; T-Lymphocytes, Cytotoxic/immunology ; Virus Latency/immunology
    Language English
    Publishing date 2015-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2278004-X
    ISSN 1934-6069 ; 1931-3128
    ISSN (online) 1934-6069
    ISSN 1931-3128
    DOI 10.1016/j.chom.2015.01.008
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  9. Article ; Online: Studies of retroviral infection in humanized mice.

    Marsden, Matthew D / Zack, Jerome A

    Virology

    2015  Volume 479-480, Page(s) 297–309

    Abstract: Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been ... ...

    Abstract Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research.
    MeSH term(s) Animals ; Disease Models, Animal ; Host-Pathogen Interactions ; Humans ; Mice, SCID ; Retroviridae/growth & development ; Retroviridae/pathogenicity ; Retroviridae/physiology ; Retroviridae Infections/pathology ; Retroviridae Infections/virology ; Virus Latency ; Virus Replication
    Language English
    Publishing date 2015-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 200425-2
    ISSN 1096-0341 ; 0042-6822
    ISSN (online) 1096-0341
    ISSN 0042-6822
    DOI 10.1016/j.virol.2015.01.017
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  10. Article ; Online: Neutralizing the HIV reservoir.

    Marsden, Matthew D / Zack, Jerome A

    Cell

    2014  Volume 158, Issue 5, Page(s) 971–972

    Abstract: Halper-Stromberg et al. use a humanized mouse model to demonstrate that broadly neutralizing antibodies, when administered with a combination of HIV latency activators, can reduce persistent HIV reservoirs, as measured by plasma virus rebound. Their ... ...

    Abstract Halper-Stromberg et al. use a humanized mouse model to demonstrate that broadly neutralizing antibodies, when administered with a combination of HIV latency activators, can reduce persistent HIV reservoirs, as measured by plasma virus rebound. Their results support the use of broadly neutralizing antibodies in HIV-reservoir-purging strategies.
    MeSH term(s) Animals ; Antibodies, Neutralizing/administration & dosage ; HIV Infections/immunology ; HIV-1/drug effects ; Humans ; Transcription, Genetic/drug effects ; Virus Latency/drug effects
    Chemical Substances Antibodies, Neutralizing
    Language English
    Publishing date 2014-08-05
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2014.08.010
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