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Viruses
Special Issues
Non-human Primate Models of Viral and Autoimmune Diseases
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Non-human Primate Models of Viral and Autoimmune Diseases

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 12007

Special Issue Editors

Dr. Karol Sestak

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Guest Editor
Tulane National Primate Research Center and PreCliniTria, LLC., Covington, LA, USA
Interests: enteric virology; mucosal immunity; gut microbiome; vaccine development; primate models; autoimmunity
Dr. Mahesh Mohan

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Guest Editor
Southwest National Primate Research Center, Texas Biomedical Research Institute, 8715 W. Military Dr., San Antonio, TX 78227, USA
Interests: HIV/SIV pathogenesis; gastrointestinal inflammation; non-human primate models; cannabinoid biology; endocannabinoid signaling; microbiome

Special Issue Information

Dear Colleagues,

Due to their phylogenetic proximity and biologic similarity to humans, non-human primates (NHPs) are increasingly being used in biomedical research involving a wide range of diseases. The evolutionary closeness of NHPs to humans and the fact that they live under similar conditions makes them premier animal models for the study of human disease. NHP models facilitated key discoveries in the areas of HIV/AIDS, genetics/genomics, neuroscience, aging, regenerative medicine, and infectious diseases in general, to name just a few. The focus of this Special Issue is on virology and autoimmunity. Studies that place emphasis on disease pathogenesis, genetics, transcriptomics, proteomics, epigenetics, virus transmission, diagnostics, prevention, novel vaccines, therapeutic development, microbiome changes, metabolome profiling, or pre-clinical validation are welcome. The purpose of this Special Issue is to encourage new and established investigators affiliated with either academic or commercial entities that utilize NHP disease models to publish novel translational findings.

Dr. Karol Sestak
Dr. Mahesh Mohan
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

  • virus
  • autoimmunity
  • primate model
  • pathogenesis
  • immune response
  • vaccine
  • therapy
  • antibody
  • simian
  • rhesus

Published Papers (4 papers)

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Research

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13 pages, 1494 KiB  
Article
A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART
by Megan A. O’Connor, Paul V. Munson, Sandra E. Dross, Hillary C. Tunggal, Thomas B. Lewis, Jessica Osborn, Christopher W. Peterson, Meei-Li W. Huang, Cassandra Moats, Jeremy Smedley, Keith R. Jerome, Hans-Peter Kiem, Kenneth C. Bagley, James I. Mullins and Deborah Heydenburg Fuller
Viruses 2021, 13(8), 1609; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081609 - 14 Aug 2021
Viewed by 3057
Abstract
Selection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the [...] Read more.
Selection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the NHP model for AIDS could influence outcomes in studies investigating interventions. Previously, in rhesus macaques (RMs) we showed that maintenance of mucosal Th17/Treg homeostasis during SIV infection correlated with a better virological response to cART. Here, in RMs we compared viral kinetics and dysregulation of gut homeostasis, defined by T cell subset disruption, during highly pathogenic SIVΔB670 compared to SHIV-1157ipd3N4 infection. SHIV infection resulted in lower acute viremia and less disruption to gut CD4 T-cell homeostasis. Additionally, 24/24 SHIV-infected versus 10/19 SIV-infected animals had sustained viral suppression <100 copies/mL of plasma after 5 months of cART. Significantly, the more profound viral suppression during cART in a subset of SIV and all SHIV-infected RMs corresponded with less gut immune dysregulation during acute SIV/SHIV infection, defined by maintenance of the Th17/Treg ratio. These results highlight significant differences in viral control during cART and gut dysregulation in NHP AIDS models and suggest that selection of a model may impact the evaluation of candidate therapeutic interventions for HIV treatment and cure strategies. Full article
(This article belongs to the Special Issue Non-human Primate Models of Viral and Autoimmune Diseases)
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15 pages, 3265 KiB  
Article
Gut Microbiome Changes Associated with Epithelial Barrier Damage and Systemic Inflammation during Antiretroviral Therapy of Chronic SIV Infection
by Ceylan Tanes, Edith M. Walker, Nadia Slisarenko, Giovanni L. Gerrets, Brooke F. Grasperge, Xuebin Qin, S. Michal Jazwinski, Frederic D. Bushman, Kyle Bittinger and Namita Rout
Viruses 2021, 13(8), 1567; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081567 - 08 Aug 2021
Cited by 11 | Viewed by 3075
Abstract
Gut dysbiosis is a common feature associated with the chronic inflammation of HIV infection. Toward understanding the interplay of chronic treated HIV infection, dysbiosis, and systemic inflammation, we investigated longitudinal fecal microbiome changes and plasma inflammatory markers in the nonhuman primate model. Following [...] Read more.
Gut dysbiosis is a common feature associated with the chronic inflammation of HIV infection. Toward understanding the interplay of chronic treated HIV infection, dysbiosis, and systemic inflammation, we investigated longitudinal fecal microbiome changes and plasma inflammatory markers in the nonhuman primate model. Following simian immunodeficiency virus (SIV) infection in rhesus macaques, significant changes were observed in several members of the phylum Firmicutes along with an increase in Bacteroidetes. Viral suppression with antiretroviral therapy (ART) resulted in an early but partial recovery of compositional changes and butyrate producing genes in the gut microbiome. Over the course of chronic SIV infection and long-term ART, however, the specific loss of Faecalibacterium prausnitzii and Treponema succinifaciens significantly correlated with an increase in plasma inflammatory cytokines including IL-6, G-CSF, I-TAC, and MIG. Further, the loss of T. succinifaciens correlated with an increase in circulating biomarkers of gut epithelial barrier damage (IFABP) and microbial translocation (LBP and sCD14). As F. prausnitzii and T. succinifaciens are major short-chain fatty acid producing bacteria, their sustained loss during chronic SV-ART may contribute to gut inflammation and metabolic alterations despite effective long-term control of viremia. A better understanding of the correlations between the anti-inflammatory bacterial community and healthy gut barrier functions in the setting of long-term ART may have a major impact on the clinical management of inflammatory comorbidities in HIV-infected individuals. Full article
(This article belongs to the Special Issue Non-human Primate Models of Viral and Autoimmune Diseases)
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18 pages, 3618 KiB  
Article
Aerosolized Exposure to H5N1 Influenza Virus Causes Less Severe Disease Than Infection via Combined Intrabronchial, Oral, and Nasal Inoculation in Cynomolgus Macaques
by Petra Mooij, Marieke A. Stammes, Daniella Mortier, Zahra Fagrouch, Nikki van Driel, Ernst J. Verschoor, Ivanela Kondova, Willy M. J. M. Bogers and Gerrit Koopman
Viruses 2021, 13(2), 345; https://0-doi-org.brum.beds.ac.uk/10.3390/v13020345 - 22 Feb 2021
Cited by 6 | Viewed by 2504
Abstract
Infection with highly pathogenic avian H5N1 influenza virus in humans often leads to severe respiratory disease with high mortality. Experimental infection in non-human primates can provide additional insight into disease pathogenesis. However, such a model should recapitulate the disease symptoms observed in humans, [...] Read more.
Infection with highly pathogenic avian H5N1 influenza virus in humans often leads to severe respiratory disease with high mortality. Experimental infection in non-human primates can provide additional insight into disease pathogenesis. However, such a model should recapitulate the disease symptoms observed in humans, such as pneumonia and inflammatory cytokine response. While previous studies in macaques have demonstrated the occurrence of typical lesions in the lungs early after infection and a high level of immune activation, progression to severe disease and lethality were rarely observed. Here, we evaluated a routinely used combined route of infection via intra-bronchial, oral, and intra-nasal virus inoculation with aerosolized H5N1 exposure, with or without the regular collection of bronchoalveolar lavages early after infection. Both combined route and aerosol exposure resulted in similar levels of virus replication in nose and throat and similar levels of immune activation, cytokine, and chemokine release in the blood. However, while animals exposed to H5N1 by combined-route inoculation developed severe disease with high lethality, aerosolized exposure resulted in less lesions, as measured by consecutive computed tomography and less fever and lethal disease. In conclusion, not virus levels or immune activation, but route of infection determines fatal outcome for highly pathogenic avian H5N1 influenza infection. Full article
(This article belongs to the Special Issue Non-human Primate Models of Viral and Autoimmune Diseases)
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7 pages, 698 KiB  
Brief Report
Intra-Host SARS-CoV-2 Evolution in the Gut of Mucosally-Infected Chlorocebus aethiops (African Green Monkeys)
by Lori A. Rowe, Brandon J. Beddingfield, Kelly Goff, Stephanie Z. Killeen, Nicole R. Chirichella, Alexandra Melton, Chad J. Roy and Nicholas J. Maness
Viruses 2022, 14(1), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/v14010077 - 01 Jan 2022
Cited by 5 | Viewed by 2170
Abstract
In recent months, several SARS-CoV-2 variants have emerged that enhance transmissibility and escape host humoral immunity. Hence, the tracking of viral evolutionary trajectories is clearly of great importance. Little is known about SARS-CoV-2 evolution in nonhuman primate models used to test vaccines and [...] Read more.
In recent months, several SARS-CoV-2 variants have emerged that enhance transmissibility and escape host humoral immunity. Hence, the tracking of viral evolutionary trajectories is clearly of great importance. Little is known about SARS-CoV-2 evolution in nonhuman primate models used to test vaccines and therapies and to model human disease. Viral RNA was sequenced from rectal swabs from Chlorocebus aethiops (African green monkeys) after experimental respiratory SARS-CoV-2 infection. Two distinct patterns of viral evolution were identified that were shared between all collected samples. First, mutations in the furin cleavage site that were initially present in the virus as a consequence of VeroE6 cell culture adaptation were not detected in viral RNA recovered in rectal swabs, confirming the necessity of this motif for viral infection in vivo. Three amino acid changes were also identified; ORF 1a S2103F, and spike D215G and H655Y, which were detected in rectal swabs from all sampled animals. These findings are demonstrative of intra-host SARS-CoV-2 evolution and may identify a host-adapted variant of SARS-CoV-2 that would be useful in future primate models involving SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Non-human Primate Models of Viral and Autoimmune Diseases)
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