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Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024
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Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 9906

Special Issue Editors

Dr. Cynthia Derdeyn

E-Mail Website
Guest Editor
1. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
2. Infectious Diseases and Translational Medicine Unit, Washington National Primate Research Center, Seattle, WA, USA
Interests: HIV-1; B cells; neutralizing antibodies; SIV; vaccines
Dr. Donald Sodora

E-Mail Website
Guest Editor
Seattle Children's Research Institute, Seattle, WA, USA
Interests: HIV-1 transmission; AIDS; developing new therapies and vaccines
Dr. Jennifer A. Manuzak

E-Mail Website
Guest Editor
1. Division of Immunology, Tulane National Primate Research Center, Covington, LA, USA
2. Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA
Interests: HIV; SIV; co-infections; mucosal immunity; innate immunity
Dr. Nina Derby

E-Mail Website
Guest Editor
Seattle Children's Research Institute, Seattle, WA, USA
Interests: HIV-1; SIV liver disease; innate immunity herpes simplex virus

Special Issue Information

Dear Colleagues,

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of the ongoing AIDS pandemic. HIV-1 infection is a life-long infection associated with high mortality. Currently, it is estimated that 38 million people live with HIV/AIDS worldwide, causing devastating socioeconomic consequences. Antiretroviral treatment combinations exist for viral suppression and prophylaxis, but their efficacy can be decreased by toxicity, limited access, and viral resistance. Moreover, no protective vaccination or virus eradication strategies exist. Addressing these shortcomings requires the strategic use of animal models that recapitulate the key features of HIV/AIDS, including transmission, immune responses, viral reservoirs, and pathogenesis. HIV/AIDS also occurs in the context of other globally significant human diseases, including tuberculosis and malaria, necessitating the development of robust models to dissect the complex interplay of immunopathologies. To this end, nonhuman primate models have been established using simian immunodeficiency virus (SIV) variants that exhibit clinical, immunologic, virologic, and pathogenic sequelae similar to HIV/AIDS. These models have been used extensively for studies of pathogenesis, prevention, and cures, as well as co-infections. In addition, SIV variants can cause viremic but non-pathogenic infections when replicating in their natural host species, giving an insight into how the progression to AIDS could be prolonged or avoided. Finally, for studies that target the HIV-1 envelope, SIV/HIV (SHIV) chimeras have been developed that facilitate the more reliable testing of antibody-based therapeutics and preventative strategies in nonhuman primates. Building on past findings and developing advanced tools will allow us to continue to leverage rigorous nonhuman primate models for HIV/AIDS as key components in the effort to halt the AIDS pandemic.

Dr. Cynthia Derdeyn
Dr. Donald Sodora
Dr. Jennifer A. Manuzak
Dr. Nina Derby
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • human immunodeficiency virus (HIV)
  • simian immunodeficiency virus (SIV)
  • HIV latency
  • pathogenesis
  • cure
  • vaccination
  • co-infection
  • transmission
  • nonhuman primate models
  • natural hosts
  • infectious diseases

Published Papers (7 papers)

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Research

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28 pages, 5014 KiB  
Article
Elevated Inflammation Associated with Markers of Neutrophil Function and Gastrointestinal Disruption in Pilot Study of Plasmodium fragile Co-Infection of ART-Treated SIVmac239+ Rhesus Macaques
by Sydney M. Nemphos, Hannah C. Green, James E. Prusak, Sallie L. Fell, Kelly Goff, Megan Varnado, Kaitlin Didier, Natalie Guy, Matilda J. Moström, Coty Tatum, Chad Massey, Mary B. Barnes, Lori A. Rowe, Carolina Allers, Robert V. Blair, Monica E. Embers, Nicholas J. Maness, Preston A. Marx, Brooke Grasperge, Amitinder Kaur, Kristina De Paris, Jeffrey G. Shaffer, Tiffany Hensley-McBain, Berlin Londono-Renteria and Jennifer A. Manuzakadd Show full author list remove Hide full author list
Viruses 2024, 16(7), 1036; https://doi.org/10.3390/v16071036 - 27 Jun 2024
Viewed by 1672
Abstract
Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated [...] Read more.
Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis. Full article
(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)
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15 pages, 3257 KiB  
Article
Viral Envelope Evolution in Simian–HIV-Infected Neonate and Adult-Dam Pairs of Rhesus Macaques
by Elena E. Giorgi, Hui Li, Bhavna Hora, George M. Shaw, Kshitij Wagh and Wilton B. Williams
Viruses 2024, 16(7), 1014; https://doi.org/10.3390/v16071014 - 25 Jun 2024
Viewed by 393
Abstract
We recently demonstrated that Simian–HIV (SHIV)-infected neonate rhesus macaques (RMs) generated heterologous HIV-1 neutralizing antibodies (NAbs) with broadly-NAb (bNAb) characteristics at a higher frequency compared with their corresponding dam. Here, we characterized genetic diversity in Env sequences from four neonate or adult/dam RM [...] Read more.
We recently demonstrated that Simian–HIV (SHIV)-infected neonate rhesus macaques (RMs) generated heterologous HIV-1 neutralizing antibodies (NAbs) with broadly-NAb (bNAb) characteristics at a higher frequency compared with their corresponding dam. Here, we characterized genetic diversity in Env sequences from four neonate or adult/dam RM pairs: in two pairs, neonate and dam RMs made heterologous HIV-1 NAbs; in one pair, neither the neonate nor the dam made heterologous HIV-1 NAbs; and in another pair, only the neonate made heterologous HIV-1 NAbs. Phylogenetic and sequence diversity analyses of longitudinal Envs revealed that a higher genetic diversity, within the host and away from the infecting SHIV strain, was correlated with heterologous HIV-1 NAb development. We identified 22 Env variable sites, of which 9 were associated with heterologous HIV-1 NAb development; 3/9 sites had mutations previously linked to HIV-1 Env bNAb development. These data suggested that viral diversity drives heterologous HIV-1 NAb development, and the faster accumulation of viral diversity in neonate RMs may be a potential mechanism underlying bNAb induction in pediatric populations. Moreover, these data may inform candidate Env immunogens to guide precursor B cells to bNAb status via vaccination by the Env-based selection of bNAb lineage members with the appropriate mutations associated with neutralization breadth. Full article
(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)
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17 pages, 3787 KiB  
Article
SIV Infection Is Associated with Transient Acute-Phase Steatosis in Hepatocytes In Vivo
by Nina Derby, Sreya Biswas, Sofiya Yusova, Cristina Luevano-Santos, Maria Cristina Pacheco, Kimberly A. Meyer, Brooke I. Johnson, Miranda Fischer, Katherine A. Fancher, Cole Fisher, Yohannes M. Abraham, Conor J. McMahon, Savannah S. Lutz, Jeremy V. Smedley, Benjamin J. Burwitz and Donald L. Sodora
Viruses 2024, 16(2), 296; https://doi.org/10.3390/v16020296 - 15 Feb 2024
Viewed by 1233
Abstract
Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a major cause of morbidity and mortality in HIV-infected individuals, even those receiving optimal antiretroviral therapy. Here, we utilized the SIV rhesus macaque model and advanced laparoscopic techniques for longitudinal collection of liver tissue to elucidate the [...] Read more.
Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a major cause of morbidity and mortality in HIV-infected individuals, even those receiving optimal antiretroviral therapy. Here, we utilized the SIV rhesus macaque model and advanced laparoscopic techniques for longitudinal collection of liver tissue to elucidate the timing of pathologic changes. The livers of both SIV-infected (N = 9) and SIV-naïve uninfected (N = 8) macaques were biopsied and evaluated at four time points (weeks −4, 2, 6, and 16–20 post-infection) and at necropsy (week 32). SIV DNA within the macaques’ livers varied by over 4 logs at necropsy, and liver SIV DNA significantly correlated with SIV RNA in the plasma throughout the study. Acute phase liver pathology (2 weeks post-infection) was characterized by evidence for fat accumulation (microvesicular steatosis), a transient elevation in both AST and cholesterol levels within the serum, and increased hepatic expression of the PPARA gene associated with cholesterol metabolism and beta oxidation. By contrast, the chronic phase of the SIV infection (32 weeks post-infection) was associated with sinusoidal dilatation, while steatosis resolved and concentrations of AST and cholesterol remained similar to those in uninfected macaques. These findings suggest differential liver pathologies associated with the acute and chronic phases of infection and the possibility that therapeutic interventions targeting metabolic function may benefit liver health in people newly diagnosed with HIV. Full article
(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)
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14 pages, 3076 KiB  
Article
Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161+CD8+ T Cells in SIV-Infected Rhesus Macaques
by Siva Thirugnanam, Edith M. Walker, Faith Schiro, Pyone P. Aye, Jay Rappaport and Namita Rout
Viruses 2023, 15(9), 1944; https://doi.org/10.3390/v15091944 - 18 Sep 2023
Viewed by 1678
Abstract
Previous studies have indicated that the loss of CD161-expressing CD4+ Th17 cells is linked to the progression of chronic HIV. These cells are significantly depleted in peripheral blood and gut mucosa of HIV-infected individuals, contributing to inflammation and disruption of the gut [...] Read more.
Previous studies have indicated that the loss of CD161-expressing CD4+ Th17 cells is linked to the progression of chronic HIV. These cells are significantly depleted in peripheral blood and gut mucosa of HIV-infected individuals, contributing to inflammation and disruption of the gut barrier. However, the impact of HIV infection on CD161-expressing CD8+ T cells remain unclear. Here, we examined the functions of peripheral blood and mucosal CD161+CD8+ T cells in the macaque model of HIV infection. In contrast to the significant loss of CD161+CD4+ T cells, CD161+CD8+ T cell frequencies were maintained in blood and gut during chronic SIV infection. Furthermore, gut CD161+CD8+ T cells displayed greater IL-17 production and maintained Th1-type and cytolytic functions, contrary to impaired IL-17 and granzyme-B production in CD161+CD4+ T cells of SIV-infected macaques. These results suggest that augmented Th17-type effector functions of CD161+CD8+ T cells during SIV infection is a likely mechanism to compensate for the sustained loss of gut mucosal Th17 cells. Targeting the cytokine and cytolytic effector functions of CD161+CD8+ T cells in the preclinical setting of chronic SIV infection with antiretroviral therapy has implications in the restoration of gut barrier disruption in persons with HIV infection. Full article
(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)
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Review

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45 pages, 712 KiB  
Review
Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection
by Jen Symmonds, Thaidra Gaufin, Cuiling Xu, Kevin D. Raehtz, Ruy M. Ribeiro, Ivona Pandrea and Cristian Apetrei
Viruses 2024, 16(6), 972; https://doi.org/10.3390/v16060972 - 17 Jun 2024
Viewed by 959
Abstract
Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus’s direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple [...] Read more.
Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus’s direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection. Full article
(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)
22 pages, 2353 KiB  
Review
Quantitative and Qualitative Distinctions between HIV-1 and SIV Reservoirs: Implications for HIV-1 Cure-Related Studies
by Joseph C. Mudd
Viruses 2024, 16(4), 514; https://doi.org/10.3390/v16040514 - 27 Mar 2024
Viewed by 1389
Abstract
The persistence of the latent viral reservoir is the main hurdle to curing HIV-1 infection. SIV infection of non-human primates (NHPs), namely Indian-origin rhesus macaques, is the most relevant and widely used animal model to evaluate therapies that seek to eradicate HIV-1. The [...] Read more.
The persistence of the latent viral reservoir is the main hurdle to curing HIV-1 infection. SIV infection of non-human primates (NHPs), namely Indian-origin rhesus macaques, is the most relevant and widely used animal model to evaluate therapies that seek to eradicate HIV-1. The utility of a model ultimately rests on how accurately it can recapitulate human disease, and while reservoirs in the NHP model behave quantitatively very similar to those of long-term suppressed persons with HIV-1 (PWH) in the most salient aspects, recent studies have uncovered key nuances at the clonotypic level that differentiate the two in qualitative terms. In this review, we will highlight differences relating to proviral intactness, clonotypic structure, and decay rate during ART between HIV-1 and SIV reservoirs and discuss the relevance of these distinctions in the interpretation of HIV-1 cure strategies. While these, to some degree, may reflect a unique biology of the virus or host, distinctions among the proviral landscape in SIV are likely to be shaped significantly by the condensed timeframe of NHP studies. ART is generally initiated earlier in the disease course, and animals are virologically suppressed for shorter periods before receiving interventions. Because these are experimental variables dictated by the investigator, we offer guidance on study design for cure-related studies performed in the NHP model. Finally, we highlight the case of GS-9620 (Vesatolimod), an antiviral TLR7 agonist tested in multiple independent pre-clinical studies in which virological outcomes may have been influenced by study-related variables. Full article
(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)
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32 pages, 506 KiB  
Review
Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects
by Amitinder Kaur and Monica Vaccari
Viruses 2024, 16(3), 368; https://doi.org/10.3390/v16030368 - 27 Feb 2024
Viewed by 1994
Abstract
The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the [...] Read more.
The human immunodeficiency virus (HIV) continues to pose a significant global health challenge, with millions of people affected and new cases emerging each year. While various treatment and prevention methods exist, including antiretroviral therapy and non-vaccine approaches, developing an effective vaccine remains the most crucial and cost-effective solution to combating the HIV epidemic. Despite significant advancements in HIV research, the HIV vaccine field has faced numerous challenges, and only one clinical trial has demonstrated a modest level of efficacy. This review delves into the history of HIV vaccines and the current efforts in HIV prevention, emphasizing pre-clinical vaccine development using the non-human primate model (NHP) of HIV infection. NHP models offer valuable insights into potential preventive strategies for combating HIV, and they play a vital role in informing and guiding the development of novel vaccine candidates before they can proceed to human clinical trials. Full article
(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)
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