Chronic binge alcohol and ovariectomy dysregulate omental adipose tissue metaboproteome in simian immunodeficiency virus-infected female macaques

2021 ◽  
Author(s):  
Jonquil Marie Poret ◽  
Jessie J Guidry ◽  
Liz Simon ◽  
Patricia E. Molina
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Simian Immunodeficiency Virus ◽  
People Living With Hiv ◽  
Infected Female ◽  
Omental Adipose Tissue ◽  
Immunodeficiency Virus ◽  
Z Scores ◽  
Functional Pathways

Effective antiretroviral therapy (ART) has significantly reduced mortality of people living with HIV (PLWH), and the prevalence of at-risk alcohol use is higher among PLWH. Increased survival and aging of PLWH is associated with increased prevalence of metabolic comorbidities especially among menopausal women, and adipose tissue metabolic dysregulation may be a significant contributing factor. We examined the differential effects of chronic binge alcohol (CBA) administration and ovariectomy (OVX) on the omental adipose tissue (OmAT) proteome in a subset of simian immunodeficiency virus (SIV)-infected macaques of a longitudinal parent study. Quantitative discovery-based proteomics identified 1429 differentially expressed proteins. Ingenuity Pathway Analysis (IPA) was used to calculate z-scores, or activation predictions, for functional pathways and diseases. Results revealed protein changes associated with functional pathways centered around the "OmAT metaboproteome profile". Based on z-scores, CBA did not affect functional pathways of metabolic disease but dysregulated proteins involved in AMPK signaling and lipid metabolism. OVX-mediated proteome changes were predicted to promote pathways involved in glucose- and lipid-associated metabolic disease. Proteins involved in apoptosis, necrosis, and reactive oxygen species (ROS) pathways were also predicted to be activated by OVX, and these were predicted to be inhibited by CBA. These results provide evidence for the role of ovarian hormone loss in mediating OmAT metaboproteome dysregulation in SIV and suggest that CBA modifies OVX-associated changes. In the context of OVX, CBA administration produced larger metabolic and cellular effects, which we speculate may reflect a protective role of estrogen against CBA-mediated adipose tissue injury in female SIV-infected macaques.

scholarly journals Release of Inflammatory Mediators by Human Adipose Tissue Is Enhanced in Obesity and Primarily by the Nonfat Cells: A Review

2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
John N. Fain
Keyword(s):  
Adipose Tissue ◽  
In Vitro Release ◽  
Human Adipose Tissue ◽  
Fat Cells ◽  
Omental Adipose Tissue ◽  
Subcutaneous Adipose ◽  
Circulating Levels ◽  
Pai 1

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFβ1, TNFα, IL-1β, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans.

scholarly journals Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques

PLoS ONE ◽  
2019 ◽  
Vol 14 (11) ◽  
pp. e0224082
Author(s):  
Michael Winkler ◽  
Sabine Gärtner ◽  
Lara Markus ◽  
Markus Hoffmann ◽  
Inga Nehlmeier ◽  
...  
Keyword(s):  
Virus Infection ◽  
Rhesus Macaque ◽  
Simian Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus

scholarly journals Inflammatory Role of Toll-Like Receptors in Human and Murine Adipose Tissue

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Odile Poulain-Godefroy ◽  
Olivier Le Bacquer ◽  
Pauline Plancq ◽  
Cécile Lecœur ◽  
François Pattou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Dietary Lipids ◽  
Toll Like Receptors ◽  
Fat Tissue ◽  
Omental Adipose Tissue ◽  
Adipocyte Cell ◽  
Inflammatory Processes ◽  
Insulin Responsiveness ◽  
Tlr4 Activation

It was recently demonstrated that TLR4 activation via dietary lipids triggers inflammatory pathway and alters insulin responsiveness in the fat tissue during obesity. Here, we question whether other TLR family members could participate in the TLR-mediated inflammatory processes occurring in the obese adipose tissue. We thus studied the expression of TLR1, TLR2, TLR4, and TLR6 in adipose tissue. These receptors are expressed in omental and subcutaneous human fat tissue, the expression being higher in the omental tissue, independently of the metabolic status of the subject. We demonstrated a correlation of TLRs expression within and between each depot suggesting a coregulation. Murine 3T3-L1 preadipocyte cells stimulated with Pam3CSK4 induced the expression of some proinflammatory markers. Therefore, beside TLR4, other toll-like receptors are differentially expressed in human fat tissue, and functional in an adipocyte cell line, suggesting that they might participate omental adipose tissue-related inflammation that occurs in obesity.

scholarly journals Sequential Evolution and Escape from Neutralization of Simian Immunodeficiency Virus SIVsmE660 Clones in Rhesus Macaques

2012 ◽  
Vol 86 (16) ◽  
pp. 8835-8847 ◽  
Author(s):  
Fan Wu ◽  
Ilnour Ourmanov ◽  
Takeo Kuwata ◽  
Robert Goeken ◽  
Charles R. Brown ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Lavage Fluid ◽  
Vaccine Protection ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Intravenous Inoculation

Simian immunodeficiency virus (SIV) infection of rhesus macaques has become an important surrogate model for evaluating HIV vaccine strategies. The extreme resistance to neutralizing antibody (NAb) of many commonly used strains, such as SIVmac251/239 and SIVsmE543-3, limits their potential relevance for evaluating the role of NAb in vaccine protection. In contrast, SIVsmE660 is an uncloned virus that appears to be more sensitive to neutralizing antibody. To evaluate the role of NAb in this model, we generated full-length neutralization-sensitive molecular clones of SIVsmE660 and evaluated two of these by intravenous inoculation of rhesus macaques. All animals became infected and maintained persistent viremia that was accompanied by a decline in memory CD4+T cells in blood and bronchoalveolar lavage fluid. High titers of autologous NAb developed by 4 weeks postinoculation but were not associated with control of viremia, and neutralization escape variants were detected concurrently with the generation of NAb. Neutralization escape was associated with substitutions and insertion/deletion polymorphisms in the V1 and V4 domains of envelope. Analysis of representative variants revealed that escape variants also induced NAbs within a few weeks of their appearance in plasma, in a pattern that is reminiscent of the escape of human immunodeficiency virus type 1 (HIV-1) isolates in humans. Although early variants maintained a neutralization-sensitive phenotype, viruses obtained later in infection were significantly less sensitive to neutralization than the parental viruses. These results indicate that NAbs exert selective pressure that drives the evolution of the SIV envelope and that this model will be useful for evaluating the role of NAb in vaccine-mediated protection.

scholarly journals Identification of a Subset of Human Immunodeficiency Virus Type 1 (HIV-1), HIV-2, and Simian Immunodeficiency Virus Strains Able To Exploit an Alternative Coreceptor on Untransformed Human Brain and Lymphoid Cells

2003 ◽  
Vol 77 (11) ◽  
pp. 6138-6152 ◽  
Author(s):  
Samantha J. Willey ◽  
Jacqueline D. Reeves ◽  
Richard Hudson ◽  
Koichi Miyake ◽  
Nathalie Dejucq ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Simian Immunodeficiency Virus ◽  
Cell Lines ◽  
Chemokine Receptors ◽  
Adult Brain ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACT The chemokine receptors CCR5 and CXCR4 are the major coreceptors for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). At least 12 other chemokine receptors or close relatives support infection by particular HIV and SIV strains on CD4+ transformed indicator cell lines in vitro. However, the role of these alternative coreceptors in vivo is presently thought to be insignificant. Infection of cell lines expressing high levels of recombinant CD4 and coreceptors thus does not provide a true indication of coreceptor use in vivo. We therefore tested primary untransformed cell cultures that lack CCR5 and CXCR4, including astrocytes and brain microvascular endothelial cells (BMVECs), for naturally expressed alternative coreceptors functional for HIV and SIV infection. An adenovirus vector (Ad-CD4) was used to express CD4 in CD4− astrocytes and thus confer efficient infection if a functional coreceptor is present. Using a large panel of viruses with well-defined coreceptor usage, we identified a subset of HIV and SIV strains able to infect two astrocyte cultures derived from adult brain tissue. Astrocyte infection was partially inhibited by several chemokines, indicating a role for the chemokine receptor family in the observed infection. BMVECs were weakly positive for CD4 but negative for CCR5 and CXCR4 and were susceptible to infection by the same subset of isolates that infected astrocytes. BMVEC infection was efficiently inhibited by the chemokine vMIP-I, implicating one of its receptors as an alternative coreceptor for HIV and SIV infection. Furthermore, we tested whether the HIV type 1 and type 2 strains identified were able to infect peripheral blood mononuclear cells (PBMCs) via an alternative coreceptor. Several strains replicated in Δ32/Δ32 CCR5 PBMCs with CXCR4 blocked by AMD3100. This AMD3100-resistant replication was also sensitive to vMIP-I inhibition. The nature and potential role of this alternative coreceptor(s) in HIV infection in vivo is discussed.

scholarly journals Role of Immune Responses against the Envelope and the Core Antigens of Simian Immunodeficiency Virus SIVmne in Protection against Homologous Cloned and Uncloned Virus Challenge in Macaques

1999 ◽  
Vol 73 (10) ◽  
pp. 8201-8215 ◽  
Author(s):  
Patricia S. Polacino ◽  
Virginia Stallard ◽  
James E. Klaniecki ◽  
Sridhar Pennathur ◽  
David C. Montefiori ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Simian Immunodeficiency Virus ◽  
Transmembrane Protein ◽  
Acute Infection ◽  
Recombinant Vaccinia Virus ◽  
Recombinant Vaccinia ◽  
The Core ◽  
Immunodeficiency Virus

ABSTRACT We previously showed that envelope (gp160)-based vaccines, used in a live recombinant virus priming and subunit protein boosting regimen, protected macaques against intravenous and intrarectal challenges with the homologous simian immunodeficiency virus SIVmne clone E11S. However, the breadth of protection appears to be limited, since the vaccines were only partially effective against intravenous challenge by the uncloned SIVmne. To examine factors that could affect the breadth and the efficacy of this immunization approach, we studied (i) the effect of priming by recombinant vaccinia virus; (ii) the role of surface antigen gp130; and (iii) the role of core antigens (Gag and Pol) in eliciting protective immunity. Results indicate that (i) priming with recombinant vaccinia virus was more effective than subunit antigen in eliciting protective responses; (ii) while both gp130 and gp160 elicited similar levels of SIV-specific antibodies, gp130 was not as effective as gp160 in protection, indicating a possible role for the transmembrane protein in presenting functionally important epitopes; and (iii) although animals immunized with core antigens failed to generate any neutralizing antibody and were infected upon challenge, their virus load was 50- to 100-fold lower than that of the controls, suggesting the importance of cellular immunity or other core-specific immune responses in controlling acute infection. Complete protection against intravenous infection by the pathogenic uncloned SIVmne was achieved by immunization with both the envelope and the core antigens. These results indicate that immune responses to both antigens may contribute to protection and thus argue for the inclusion of multiple antigens in recombinant vaccine designs.

scholarly journals Role of IL-15 Signaling in the Pathogenesis of Simian Immunodeficiency Virus Infection in Rhesus Macaques

2019 ◽  
Vol 203 (11) ◽  
pp. 2928-2943
Author(s):  
Afam A. Okoye ◽  
Maren Q. DeGottardi ◽  
Yoshinori Fukazawa ◽  
Mukta Vaidya ◽  
Chike O. Abana ◽  
...  
Keyword(s):  
Virus Infection ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Simian Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus
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