Article
Cell Biology
Nongthombam Boby, Alyssa Ransom, Barcley T. Pace, Kelsey M. Williams, Christopher Mabee, Arpita Das, Sudesh K. Srivastav, Edith Porter, Bapi Pahar
Summary: Increased production of TGF-beta was observed in intestinal CD3(-)CD20(-)CD68(+) cells from SIV-infected rhesus macaques, which negatively correlated with the frequency of jejunum CD4(+) T cells. Disruption of a negative feedback loop mediated by SMAD7 may enhance TGF-beta production and SMAD-dependent signaling in SIV infection.
Article
Immunology
Nongthombam Boby, Xuewei Cao, Alyssa Ransom, Barcley T. Pace, Christopher Mabee, Monica N. Shroyer, Arpita Das, Peter J. Didier, Sudesh K. Srivastav, Edith Porter, Qiuying Sha, Bapi Pahar
Summary: Research has shown that under SIV infection, intestinal epithelial regeneration decreases, certain cell types increase, and differentially expressed genes in important pathways are downregulated. Despite the lack of significant reduction in stem cell population, dysregulation of intestinal stem cell niche factors, presence of inflammatory factors, and loss of epithelial barrier function, suggest that SIV infection impacts epithelial cell proliferation and intestinal homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Saori Matsuoka, Takeo Kuwata, Hiroshi Ishii, Tsuyoshi Sekizuka, Makoto Kuroda, Masato Sano, Midori Okazaki, Hiroyuki Yamamoto, Mikiko Shimizu, Shuzo Matsushita, Yohei Seki, Akatsuki Saito, Hiromi Sakawaki, Vanessa M. Hirsch, Tomoyuki Miura, Hirofumi Akari, Tetsuro Matano
Summary: This study found a potent antibody induction associated with germ line BCR/antibody Ig gene polymorphism in rhesus macaques infected with SIV. The results demonstrate that a single nucleotide polymorphism in germ line Ig genes could be a determinant for induction of potent antibodies against virus infection. Germ line BCR/antibody Ig gene polymorphisms may be a factor restricting effective antibody induction or responsiveness to vaccination.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams
Summary: Despite effective antiretroviral therapy, comorbidities such as neurocognitive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. This study investigates the co-development of cardiac pathology and CNS pathology in SIV-infected rhesus macaques, demonstrating a strong correlation with activated myeloid cells. Similar observations were confirmed in HIV-infected individuals, highlighting the need for adjunctive therapies targeting macrophages.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Dan Liu, Jiaojiao Liu, Tingting Xu, Hongwei Qiao, Yu Qi, Yuxun Gao, Ailixire, Lei Gao, Chunlin Li, Mingrui Xia, Hongjun Li
Summary: Using SIV-infected macaques as a model, this study found brain volume changes at 12 weeks post-infection in various brain regions. Despite early initiation of cART after SIV infection, brain atrophy in macaques was still observed, with signs of potential reversibility. Plasma viral load was associated with subcortical nucleus volume, while CD4(+) T-cell count and CD4(+)/CD8(+) ratio in plasma were linked to widespread cortical volume changes.
Article
Virology
Bapi Pahar, Wayne Gray, Marissa Fahlberg, Brooke Grasperge, Meredith Hunter, Arpita Das, Christopher Mabee, Pyone Pyone Aye, Faith Schiro, Krystle Hensley, Aneeka Ratnayake, Kelly Goff, Celia LaBranche, Xiaoying Shen, Georgia D. Tomaras, C. Todd DeMarco, David Montefiori, Patricia Kissinger, Preston A. Marx, Vicki Traina-Dorge
Summary: By using a varicella virus-vectored SIV vaccine and protein boosts, this study demonstrated a 37.5% efficacy rate against pathogenic SIV challenge in a rhesus macaque model by generating neutralizing antibodies, binding antibodies, and polyfunctional T-cell responses.
Article
Medicine, Research & Experimental
Benjamin D. Varco-Merth, William Brantley, Alejandra Marenco, Derick D. Duell, Devin N. Fachko, Brian Richardson, Kathleen Busman-Sahay, Danica Shao, Walter Flores, Kathleen Engelman, Yoshinori Fukazawa, Scott W. Wong, Rebecca L. Skalsky, Jeremy Smedley, Michael K. Axthelm, Jeffrey D. Lifson, Jacob D. Estes, Paul T. Edlefsen, Louis J. Picker, Cheryl M. A. Cameron, Timothy J. Henrich, Afam A. Okoye
Summary: Inhibiting mTOR can decrease the proliferation of CD4(+)TM cells, but chronic mTOR inhibition alone or in combination with T cell activation is not sufficient to disrupt the stability of the SIV reservoir.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Virology
Widade Ziani, Anya Bauer, Hong Lu, Xiaolei Wang, Xueling Wu, Katharine J. Bar, Hui Li, Dongfang Liu, George M. Shaw, Ronald S. Veazey, Huanbin Xu
Summary: The newly developed SHIV.C.CH848 can establish sustained viremia and viral reservoirs in rhesus macaques with clinical immunodeficiency consequences, providing a valuable SHIV model for HIV research. The findings suggest that this CCR5-tropic, SHIVC strain is valuable for testing responses to HIV vaccines and therapeutics in nonhuman primate models.
JOURNAL OF VIROLOGY
(2021)
Article
Microbiology
Anya Bauer, Emily Lindemuth, Francesco Elia Marino, Ryan F. Krause, Jaimy Joy, Steffen P. Docken, Suvadip Mallick, Kevin M. McCormick, Clinton J. Holt, Ivelin A. Georgiev, Barbara C. Felber, Brandon A. Keele, Ronald C. Veazey, Miles A. Davenport, Hui C. Li, George A. Shaw, Katharine C. Bar
Summary: This study reported the generation of a minimally adapted virus, SHIV.C.CH505.v2, which has enhanced replication fitness and preserved native Env properties. It can be used as a new reagent for nonhuman primate studies of HIV-1 transmission, pathogenesis, and cure.
Article
Obstetrics & Gynecology
Jason C. Hedges, Carol B. Hanna, Jasper C. Bash, Emily R. Boniface, Fernanda C. Burch, Shruthi Mahalingaiah, Victoria H. J. Roberts, Juanito Jose D. Terrobias, Emily C. Mishler, Jared V. Jensen, Charles A. Easley, Jamie O. Lo
Summary: Chronic exposure to THC in nonhuman primates resulted in testicular atrophy, increased serum gonadotropin levels, and decreased serum sex steroid levels, suggesting primary testicular failure.
FERTILITY AND STERILITY
(2022)
Article
Obstetrics & Gynecology
Jason C. Hedges, Carol B. Hanna, Lyndsey E. Shorey-Kendrick, Emily R. Boniface, Jasper C. Bash, Travis L. Rice-Stitt, Fernanda C. Burch, Rahul D'Mello, Terry K. Morgan, Ana Cristina Lima, Juanito Jose D. Terrobias, Jason A. Graham, Emily C. Mishler, Jared V. Jensen, Olivia L. Hagen, J. Wes Urian, Eliot R. Spindel, Charles A. Easley, Susan K. Murphy, Jamie O. Lo
Summary: This study used rhesus macaques as the animal model to investigate the effects of THC on male reproductive health and whether discontinuation of THC use can mitigate these effects. The results showed that chronic THC use caused testicular atrophy, decreased sex hormone levels, and changes in semen parameters, while these effects were partially restored after discontinuation of THC use.
FERTILITY AND STERILITY
(2023)
Article
Immunology
Naofumi Takahashi, Amir Ardeshir, Gerard E. Holder, Yanhui Cai, Chie Sugimoto, Kazuyasu Mori, Mariluz Arainga, Ziyuan He, Yayoi Fukuyo, Woong-Ki Kim, Elizabeth S. Didier, Marcelo J. Kuroda
Summary: Increased monocyte turnover was found to have a stronger correlation and contribution to decreased survival time in SIV/SHIV-infected rhesus macaques compared to CD4(+) T-cell decline, plasma viral load, or virus strain. A monocyte turnover rate of 13.2% was identified as the initial significant threshold that best predicted decreased survival time.
Article
Behavioral Sciences
Julian B. Hattler, Derek L. Irons, Jiangtao Luo, Woong-Ki Kim
Summary: This study found that in the brain during SIV pathogenesis, there was an increase in the number of CCR5+ CD8 T cells and a downregulated CCR5 expression on infected PVMs, likely through ERK1/2-driven, clathrin-mediated endocytosis.
BRAIN AND BEHAVIOR
(2023)
Article
Substance Abuse
L. Jenny Wiley, I. Shanequa Taylor, A. Julie Marusich
Summary: The study examined the effects of THC administered through different routes on rats. Results showed varying effects of THC across different routes of administration, providing empirical evidence for choosing the route of administration for mechanistic investigation of THC's pharmacology. Animal models using translationally relevant routes of administration may lead to more accurate predictions of THC effects in humans.
DRUG AND ALCOHOL DEPENDENCE
(2021)
Article
Behavioral Sciences
Antony D. Abraham, Jenny L. Wiley, Julie A. Marusich
Summary: This study found that THC has an impact on nicotine intake in rat models, decreasing self-administration of nicotine and altering the dose-effect curve. Unlike nicotine, THC does not affect the response to sucrose.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2023)
Review
Physiology
Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina
Summary: At-risk alcohol use contributes significantly to the global healthcare burden, leading to preventable diseases and deaths. Understanding the mechanisms of alcohol-induced tissue injury is crucial for the development of effective interventions. This article provides a comprehensive review of the current knowledge on the pathophysiological mechanisms involved in alcohol-related tissue damage.
ANNUAL REVIEW OF PHYSIOLOGY
(2022)
Article
Critical Care Medicine
Alejandra Jacotte-Simancas, Jason W. Middleton, Zachary F. Stielper, Scott Edwards, Patricia E. Molina, Nicholas W. Gilpin
Summary: TBI produces sex-specific acute effects on BLA neuronal activation, excitability, and synaptic transmission. Females exhibit increased apnea duration and reduced respiratory rate post-TBI relative to males. In both male and female rats, TBI increases c-fos expression in BLA glutamatergic cells and firing rate in BLA pyramidal neurons. In females, TBI also increases spontaneous excitatory and inhibitory postsynaptic current amplitude and sEPSC frequency in BLA neurons.
JOURNAL OF NEUROTRAUMA
(2022)
Article
Cell Biology
Brianna L. Bourgeois, Hui-Yi Lin, Alice Y. Yeh, Danielle E. Levitt, Stefany D. Primeaux, Tekeda F. Ferguson, Patricia E. Molina, Liz Simon
Summary: People living with HIV (PLWH) have increased prevalence of comorbid conditions including insulin resistance and at-risk alcohol use. Circulating microRNAs (miRs) may serve as minimally invasive indicators of pathophysiological states. This study aimed to identify whether alcohol modulates circulating miR associations with measures of glucose/insulin dynamics in PLWH.
PHYSIOLOGICAL GENOMICS
(2022)
Review
Physiology
Liz Simon, Scott Edwards, Patricia E. Molina
Summary: At-risk alcohol use has significant negative effects on multiple bodily systems, especially in vulnerable populations like PLWH. This review explores the mechanisms by which alcohol exacerbates cardiometabolic and neuropathological comorbidities, highlighting the impact of environmental factors.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Substance Abuse
Jerry S. Zifodya, Tekeda F. Ferguson, Robert W. Siggins, Meghan M. Brashear, Stephen P. Kantrow, Steve Nelson, Judd E. Shellito, Patricia E. Molina, David A. Welsh
Summary: People living with HIV (PLWH) are at increased risk for noncommunicable diseases such as lung disease, and alcohol use disorder (AUD) is common in PLWH and associated with higher risk of pneumonia. This study found no association between total lifetime alcohol use or early life alcohol use and pulmonary function in PLWH, but current heavy alcohol use was associated with impaired pulmonary function.
Article
Immunology
Patrick M. McTernan, Danielle E. Levitt, David A. Welsh, Liz Simon, Robert W. Siggins, Patricia E. Molina
Summary: This study found that ethanol disrupts CD4(+) T cell differentiation, increasing pro-inflammatory cells and decreasing immunosuppressive cells, as well as affecting CD4(+) T cell immunometabolism and impairing mitochondrial repair processes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Patrick M. McTernan, Robert W. Siggins, Anna Catinis, Angela M. Amedee, Liz Simon, Patricia E. Molina
Summary: Effective antiretroviral therapy has turned HIV into a chronic disease, leading to a growing population of people over 50 living with HIV. Animal experiments have shown that chronic binge alcohol consumption and ovariectomy result in increased expression of SIV co-receptors in peripheral activated CD4(+) T cells and dysregulation of mitochondrial homeostasis.
Article
Substance Abuse
Danielle E. Levitt, Liz Simon, Hui-Yi Lin, Robert W. Siggins, Tekeda F. Ferguson, Patricia E. Molina, David A. Welsh
Summary: This study investigated the relationship between body composition and frailty risk among people living with HIV. The results showed that higher fat-free mass index and body fat percentage were associated with decreased frailty risk, while obesity increased the risk. The study also revealed that recent alcohol use, muscle strength, and physical activity moderated the relationship between body composition and frailty risk.
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Article
Substance Abuse
Brianna L. Bourgeois, Danielle E. Levitt, Patricia E. Molina, Liz Simon
Summary: Our studies demonstrate that chronic binge alcohol (CBA) and HIV infection significantly impact metabolic homeostasis, particularly in adipose tissue and skeletal muscle. CBA alters the differentiation potential of adipose-derived stem cells and myoblasts, and the differential expression of microRNAs (miRs) contributes to impaired myoblast differentiation. CBA also modulates the concentration and miR cargo of extracellular vesicles (EVs) derived from adipocytes and myotubes in SIV-infected macaques. These findings underscore the importance of EV-mediated intercellular communication in metabolic dysregulation.
Article
Endocrinology & Metabolism
Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. McDaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J. J. Ronis
Summary: This study examines the relationship between alcohol use, bone health, and bone mass changes in people living with HIV. Through clinical data and animal experiments, the study findings suggest that alcohol consumption is associated with alterations in bone morphology and density, and age and menopausal status increase the susceptibility to these effects.
Article
Immunology
Michael G. Dubic, Scott Edwards, Lee S. McDaniel, Liz Simon, Patricia E. Molina
Summary: People living with HIV are more likely to engage in risky alcohol use and are at higher risk of neurocognitive decline. This study explored the mechanisms underlying HIV-associated neurocognitive disorder (HAND) and found that chronic binge alcohol consumption may increase neuroinflammatory gene expression and decrease growth factor signaling. Additionally, gene expression patterns in peripheral blood mononuclear cells (PBMCs) may reflect expression changes in the brain. These findings are important for understanding HAND related to alcohol use and HIV exposure.
AIDS RESEARCH AND HUMAN RETROVIRUSES
(2023)
Review
Biochemistry & Molecular Biology
Robert W. Siggins, Patrick M. McTernan, Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina
Summary: Alcohol misuse negatively affects tissues involved in energy metabolism regulation, such as the liver, pancreas, adipose, and skeletal muscle. It impairs mitochondrial functions and disrupts immunometabolism, leading to tissue injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Flavia M. Souza-Smith, Patricia E. Molina, Rajani Maiya
Summary: Chronic alcohol consumption in rodents leads to hyperpermeability of mesenteric collecting lymphatic vessels, lymph leakage, and immunometabolic dysregulation of perilymphatic adipose tissue (PLAT). This study aimed to investigate the alcohol-induced changes in lymph and plasma proteome using quantitative proteomic analysis. The results identified upregulation of apolipoproteins in lymph from alcohol-fed animals and downregulation of proteins in the plasma of alcohol-fed animals. Network analysis also revealed differentially expressed hub proteins in the lymph, while plasma analysis showed a module with no significant enrichment of differentially expressed proteins. Further studies will explore the functionality of these hub proteins in both lymph and plasma.
Article
Cell Biology
Kelly C. Cunningham, Deandra R. Smith, Daniel N. Villageliu, Christi M. Ellis, Amanda E. Ramer-Tait, Jeffrey D. Price, Todd A. Wyatt, Daren L. Knoell, Mystera M. Samuelson, Patricia E. Molina, David A. Welsh, Derrick R. Samuelson
Summary: Chronic alcohol abuse leads to alterations in the gastrointestinal microbiota, resulting in behavior changes, physiological alterations, and immunological effects. This study developed a humanized alcohol-microbiota mouse model and found that colonization of mice with fecal microbiota from individuals with high AUDIT scores increased susceptibility to pneumonia.
Article
Substance Abuse
Shawn M. Cohen, Dominick Dephilippis, Yanhong Deng, James Dziura, Tekeda Ferguson, Lisa M. Fucito, Amy C. Justice, Stephen Maisto, Vincent C. Marconi, Patricia Molina, Manuel Paris, Maria C. Rodriguez-Barradas, Michael Simberkoff, Nancy M. Petry, David A. Fiellin, E. Jennifer Edelman
Summary: This study evaluated perspectives on implementing contingency management (CM) to address unhealthy alcohol use for people with HIV in primary care settings. CM was viewed as a helpful, positive, and feasible approach to addressing unhealthy alcohol use and related conditions among patients and staff involved in a clinical trial. To enhance implementation, future efforts may consider simplified approaches to the reward structure and expanding rewards to non-abstinent reductions in alcohol consumption.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2023)