scholarly journals Reduced neuronal population in the dorsolateral prefrontal cortex in infant macaques infected with simian immunodeficiency virus (SIV)

2021 ◽  
Author(s):  
Alexandra Haddad ◽  
Brittany Voth ◽  
Janiya Brooks ◽  
Melanie Swang ◽  
Heather Carryl ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Dorsolateral Prefrontal Cortex ◽  
Neuronal Population ◽  
Pediatric Hiv ◽  
Health Crisis ◽  
Immunodeficiency Virus ◽  
Dorsolateral Prefrontal ◽  
Siv Infection

AbstractPediatric HIV infection remains a global health crisis with an estimated 150,000 new mother-to-child (MTCT) infections each year. Antiretroviral therapy (ART) has improved childhood survival, but only an estimated 53% of children worldwide have access to treatment. Adding to the health crisis is the neurological impact of HIV on the developing brain, in particular cognitive and executive function, which persists even when ART is available. Imaging studies suggest structural, connectivity, and functional alterations in perinatally HIV-infected youth. However, the paucity of histological data limits our ability to identify specific cortical regions that may underlie the clinical manifestations. Utilizing the pediatric simian immunodeficiency virus (SIV) infection model in infant macaques, we have previously shown that early-life SIV infection depletes the neuronal population in the hippocampus. Here, we expand on these previous studies to investigate the dorsolateral prefrontal cortex (dlPFC). A total of 11 ART-naïve infant rhesus macaques (Macaca mulatta) from previous studies were retrospectively analyzed. Infant macaques were either intravenously (IV) inoculated with highly virulent SIVmac251 at ~1 week of age and monitored for 6–10 weeks or orally challenged with SIVmac251 from week 9 of age onwards with a monitoring period of 10–23 weeks post-infection (19–34 weeks of age), and SIV-uninfected controls were euthanized at 16–17 weeks of age. Both SIV-infected groups show a significant loss of neurons along with evidence of ongoing neuronal death. Oral- and IV-infected animals showed a similar neuronal loss which was negatively correlated to chronic viremia levels as assessed by an area under the curve (AUC) analysis. The loss of dlPFC neurons may contribute to the rapid neurocognitive decline associated with pediatric HIV infection.

scholarly journals Immunization of Newborn Rhesus Macaques with Simian Immunodeficiency Virus (SIV) Vaccines Prolongs Survival after Oral Challenge with Virulent SIVmac251

2003 ◽  
Vol 77 (1) ◽  
pp. 179-190 ◽  
Author(s):  
Koen K. A. Van Rompay ◽  
Jennifer L. Greenier ◽  
Kelly Stefano Cole ◽  
Patricia Earl ◽  
Bernard Moss ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Disease Free Survival ◽  
Active Immunization ◽  
Pediatric Hiv ◽  
Maternal Antibodies ◽  
Immunization Strategies ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus

ABSTRACT There is an urgent need for active immunization strategies that, if administered shortly after birth, could protect infants in developing countries from acquiring human immunodeficiency virus (HIV) infection through breast-feeding. Better knowledge of the immunogenic properties of vaccine candidates in infants and of the effect of maternal antibodies on vaccine efficacy will aid in the development of such a neonatal HIV vaccine. Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model of pediatric HIV infection with which to address these questions. Groups of infant macaques were immunized at birth and 3 weeks of age with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol, and Env (MVA-SIVgpe) or live-attenuated SIVmac1A11. One MVA-SIVgpe-immunized group had maternally derived anti-SIV antibodies prior to immunization. Animals were challenged orally at 4 weeks of age with a genetically heterogeneous stock of virulent SIVmac251. Although all animals became infected, the immunized animals mounted better antiviral antibody responses, controlled virus levels more effectively, and had a longer disease-free survival than the unvaccinated infected monkeys. Maternal antibodies did not significantly reduce the efficacy of the MVA-SIVgpe vaccine. In conclusion, although the tested vaccines delayed the onset of AIDS, further studies are warranted to determine whether a vaccine that elicits stronger early immune responses at the time of virus exposure may be able to prevent viral infection or AIDS in infants.

scholarly journals Magnitude and Quality of Cytokine and Chemokine Storm during Acute Infection Distinguish Nonprogressive and Progressive Simian Immunodeficiency Virus Infections of Nonhuman Primates

2016 ◽  
Vol 90 (22) ◽  
pp. 10339-10350 ◽  
Author(s):  
Sheila M. Keating ◽  
John W. Heitman ◽  
Shiquan Wu ◽  
Xutao Deng ◽  
Andrea R. Stacey ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Acute Phase ◽  
Area Under The Curve ◽  
Host Immune System ◽  
Amyloid A ◽  
Infection Models ◽  
Serum Amyloid A Protein ◽  
Immunodeficiency Virus ◽  
Siv Infection

ABSTRACTAcute human immunodeficiency virus (HIV) infection represents a period of intense immune perturbation and activation of the host immune system. Study of the eclipse and viral expansion phases of infection is difficult in humans, but studies in nonprogressive and progressive nonhuman primate (NHP) infection models can provide significant insight into critical events occurring during this time. Cytokines, chemokines, and other soluble immune factors were measured in longitudinal samples from rhesus macaques infected with either SIVmac251 (progressive infection) or SIVmac239Δnef(attenuated/nonprogressive infection) and from African green monkeys infected with SIVsab9315BR (nonpathogenic infection). Levels of acute-phase peak viral replication were highest in SIVmac251 infection but correlated positively with viremia at 3 months postinfection in all three infection models. SIVmac251 infection was associated with stronger corresponding acute-phase cytokine/chemokine responses than the nonprogressive infections. The production of interleukin 15 (IL-15), IL-18, gamma interferon (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1β (MIP-1β), and serum amyloid A protein (SAA) during acute SIVmac251 infection, but not during SIVmac239Δnefor SIVsab9315BR infection, correlated positively with chronic viremia at 3 months postinfection. Acute-phase production of MCP-1 correlated with viremia at 3 months postinfection in both nonprogressive infections. Finally, a positive correlation between the acute-phase area under the curve (AUC) for IL-6 and soluble CD40 ligand (sCD40L) and chronic viremia was observed only for the nonprogressive infection models. While we observed dynamic acute inflammatory immune responses in both progressive and nonprogressive SIV infections, the responses in the nonprogressive infections were not only lower in magnitude but also qualitatively different biomarkers of disease progression.IMPORTANCENHP models of HIV infection constitute a powerful tool with which to study viral pathogenesis in order to gain critical information for a better understanding of HIV infection in humans. Here we studied progressive and nonprogressive simian immunodeficiency virus (SIV) infection models in both natural and nonnatural host NHP species. Regardless of the pathogenicity of the virus infection and regardless of the NHP species studied, the magnitude of viremia, as measured by area under the curve, during the first 4 weeks of infection correlated positively with viremia in chronic infection. The magnitude of cytokine and chemokine responses during primary infection also correlated positively with both acute-phase and chronic viremia. However, the pattern and levels of specific cytokines and chemokines produced differed between nonprogressive and progressive SIV infection models. The qualitative differences in the early immune response in pathogenic and nonpathogenic infections identified here may be important determinants of the subsequent disease course.

scholarly journals Gastrointestinal Tract and the Mucosal Macrophage Reservoir in HIV Infection

2014 ◽  
Vol 21 (11) ◽  
pp. 1469-1473 ◽  
Author(s):  
Dallas Brown ◽  
Joseph J. Mattapallil
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Gastrointestinal Tract ◽  
Hiv Infection ◽  
Simian Immunodeficiency Virus ◽  
Primary Site ◽  
Functional Cure ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Explosive Phase

ABSTRACTThe gastrointestinal tract (GIT) is a primary site for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection, replication, and dissemination. After an initial explosive phase of infection, HIV establishes latency. In addition to CD4 T cells, macrophages are readily infected, which can persist for long periods of time. Though macrophages at various systemic sites are infected, those present in the GIT constitute a major cellular reservoir due to the abundance of these cells at mucosal sites. Here, we review some of the important findings regarding what is known about the macrophage reservoir in the gut and explore potential approaches being pursued in the field to reduce this reservoir. The development of strategies that can lead to a functional cure will need to incorporate approaches that can eradicate the macrophage reservoir in the GIT.

scholarly journals New ways of preventing HIV infection: thinking simply, simply thinking

2006 ◽  
Vol 361 (1469) ◽  
pp. 811-820 ◽  
Author(s):  
R.V Short
Keyword(s):  
Clinical Trials ◽  
Hiv Infection ◽  
Oral Contraceptive Pill ◽  
Lemon Juice ◽  
Health Crisis ◽  
Main Site ◽  
Susceptibility To Infection ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Hiv Entry

HIV infection is the greatest health crisis in human history. It continues to spread unchecked among the poor in the developing world because we have failed to design simple preventative methods that are available and affordable to those living on under $2 a day. Five new methods are discussed. (i) A natural microbicide . Intravaginal lime or lemon juice has been used for centuries as a traditional contraceptive. The juice can also kill HIV in the laboratory, but clinical trials are needed to see if vaginal application is acceptable, safe and effective. (ii) Intravaginal oestrogen . Monkeys can be protected from Simian immunodeficiency virus (SIV) infection by keratinizing the vagina with topical oestrogen. If women take the oral contraceptive pill vaginally it retains its contraceptive efficacy, and the oestrogen it contains should thicken the vagina and protect against HIV infection. Clinical trials are needed. (iii) Male circumcision . Removal of the inner foreskin removes the main site of HIV entry into the penis, resulting in a sevenfold reduction in susceptibility to infection. The practice needs to be promoted. (iv) Post-coital penile hygiene . Wiping the penis immediately after intercourse with lime or lemon juice or vinegar should kill the virus before it has had a chance to infect. A clinical trial of efficacy is needed. (v) PhotoVoice . Asking schoolchildren in developing countries to photograph their impressions of HIV/AIDS is a powerful way of getting them to discuss the subject openly, and develop their own preventative strategies.

scholarly journals Enhanced Intestinal TGF-β/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 806
Author(s):  
Nongthombam Boby ◽  
Alyssa Ransom ◽  
Barcley T. Pace ◽  
Kelsey M. Williams ◽  
Christopher Mabee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Simian Immunodeficiency Virus ◽  
Transforming Growth Factor ◽  
Rhesus Macaques ◽  
Transforming Growth Factor Β ◽  
Immunodeficiency Virus ◽  
Cellular Source ◽  
Siv Infection ◽  
Β Receptor ◽  
Differentiation And Proliferation

Transforming growth factor-β signaling (TGF-β) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either SMAD2/3 and SMAD7 (SMAD-dependent) or SMAD-independent signaling pathways under normal conditions. Increased production of TGF-β promotes immunosuppression in Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection. However, the cellular source and downstream events of increased TGF-β production that attributes to its pathological manifestations remain unknown. Here, we have shown increased production of TGF-β in a majority of intestinal CD3−CD20−CD68+ cells from acute and chronically SIV infected rhesus macaques, which negatively correlated with the frequency of jejunum CD4+ T cells. No significant changes in intestinal TGF-β receptor II expression were observed but increased production of the pSMAD2/3 protein and SMAD3 gene expression in jejunum tissues that were accompanied by a downregulation of SMAD7 protein and gene expression. Enhanced TGF-β production by intestinal CD3−CD20−CD68+ cells and increased TGF-β/SMAD-dependent signaling might be due to a disruption of a negative feedback loop mediated by SMAD7. This suggests that SIV infection impacts the SMAD-dependent signaling pathway of TGF-β and provides a potential framework for further study to understand the role of viral factor(s) in modulating TGF-β production and downregulating SMAD7 expression in SIV. Regulation of mucosal TGF-β expression by therapeutic TGF-β blockers may help to create effective antiviral mucosal immune responses.

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