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
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
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
Medicine, Research & Experimental
Augusto F. Schmidt, Daniel J. Schnell, Kenneth P. Eaton, Kashish Chetal, Paranthaman S. Kannan, Lisa A. Miller, Claire A. Chougnet, Daniel T. Swarr, Alan H. Jobe, Nathan Salomonis, Beena D. Kamath-Rayne
Summary: Accurate estimation of fetal maturity can provide personalized guidance for complicated pregnancies. In this study, transcriptomic profiling of lung and brain in rhesus macaque fetuses identified potential new and previously associated gestational age differences. Furthermore, the use of antenatal corticosteroids had off-target effects on brain development. Cell-free RNA in amniotic fluid may serve as global fetal maturation markers for personalized management of at-risk pregnancies.
Article
Pharmacology & Pharmacy
Brandi N. Williamson, Lizzette Perez-Perez, Benjamin Schwarz, Friederike Feldmann, Myndi G. Holbrook, Manmeet Singh, Diane S. Lye, Darius Babusis, Raju Subramanian, Elaine Haddock, Atsushi Okumura, Patrick W. Hanley, Jamie Lovaglio, Catharine M. Bosio, Danielle P. Porter, Tomas Cihlar, Richard L. Mackman, Greg Saturday, Emmie De Wit
Summary: This study demonstrates that early subcutaneous administration of remdesivir can reduce the risk of lower respiratory tract disease caused by SARS-CoV-2 infection.
ANTIVIRAL RESEARCH
(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
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
Virology
Antonio Solis-Leal, Summer Siddiqui, Fei Wu, Mahesh Mohan, Wenhui Hu, Lara A. Doyle-Meyers, Jason P. Dufour, Binhua Ling
Summary: The basal ganglia in SIV-infected chRMs have a high frequency of SIV even on ART, indicating ongoing neuroinflammation. Plasma CCL2 may serve as a biomarker for neuroinflammation.
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
Immunology
Carolina Garrido, Alan D. Curtis, Maria Dennis, Sachi H. Pathak, Hongmei Gao, David Montefiori, Mark Tomai, Christopher B. Fox, Pamela A. Kozlowski, Trevor Scobey, Jennifer E. Munt, Michael L. Mallory, Pooja T. Saha, Michael G. Hudgens, Lisa C. Lindesmith, Ralph S. Baric, Olubukola M. Abiona, Barney Graham, Kizzmekia S. Corbett, Darin Edwards, Andrea Carfi, Genevieve Fouda, Koen K. A. Van Rompay, Kristina De Paris, Sallie R. Permar
Summary: The study evaluated the safety and immunogenicity of two SARS-CoV-2 vaccines in infant Rhesus macaques, showing that both vaccines were well-tolerated and highly immunogenic. The vaccines elicited high levels of antibodies and cellular immune responses that persisted up to week 22, indicating the potential for a pediatric SARS-CoV-2 vaccine with durable immunity.
SCIENCE IMMUNOLOGY
(2021)
Article
Virology
Sanath Kumar Janaka, Brian J. Snow, Ryan T. Behrens, David T. Evans
Summary: Tetherin is a protein that prevents viruses from detaching from infected cells by physically tethering them to cellular membranes. SIV Nef downmodulates simian tetherin to overcome this restriction in nonhuman primate hosts. In addition to counteracting tetherin, SIV Nef has a number of other functions, including downmodulating other proteins from the cell surface. Researchers have engineered an infectious molecular clone of SIV with substitutions in Nef that separate tetherin antagonism from other Nef functions. This study demonstrates the importance of tetherin antagonism for optimal replication of SIV in primary CD4(+) T cells.
JOURNAL OF VIROLOGY
(2022)
Article
Virology
Philip R. Tedbury, Mariia Novikova, Ayna Alfadhli, Yuta Hikichi, Ioannis Kagiampakis, Vineet N. KewalRamani, Eric Barklis, Eric O. Freed
JOURNAL OF VIROLOGY
(2020)
Article
Virology
Kevin Melody, Chandra N. Roy, Christopher Kline, Mackenzie L. Cottrell, Dwayne Evans, Kathleen Shutt, Pleuni S. Pennings, Brandon F. Keele, Moses Bility, Angela D. M. Kashuba, Zandrea Ambrose
JOURNAL OF VIROLOGY
(2020)
Article
Microbiology
Wen Li, Parmit K. Singh, Gregory A. Sowd, Gregory J. Bedwell, Sooin Jang, Vasudevan Achuthan, Amarachi V. Oleru, Doris Wong, Hind J. Fadel, KyeongEun Lee, Vineet N. KewalRamani, Eric M. Poeschla, Alon Herschhorn, Alan N. Engelmana
Article
Cell Biology
Anastasia Selyutina, Mirjana Persaud, Kyeongeun Lee, Vineet KewalRamani, Felipe Diaz-Griffero
Article
Biochemistry & Molecular Biology
Chaoyi Xu, Douglas K. Fischer, Sanela Rankovic, Wen Li, Robert A. Dick, Brent Runge, Roman Zadorozhnyi, Jinwoo Ahn, Christopher Aiken, Tatyana Polenova, Alan N. Engelman, Zandrea Ambrose, Itay Rousso, Juan R. Perilla
Article
Microbiology
Stephanie V. Rebensburg, Guochao Wei, Ross C. Larue, Jared Lindenberger, Ashwanth C. Francis, Arun S. Annamalai, James Morrison, Nikoloz Shkriabai, Szu-Wei Huang, Vineet KewalRamani, Eric M. Poeschla, Gregory B. Melikyan, Mamuka Kvaratskhelia
Summary: This study identified Sec24C as a host dependency factor for HIV-1 infection, showing that it facilitates viral trafficking, stability, and infectivity. The interactions between Sec24C and capsid lattices are crucial for productive infection of target cells across different cellular compartments. The study provides insights into the early events of the HIV-1 lifecycle and the role of host factors in virus-host interactions.
NATURE MICROBIOLOGY
(2021)
Article
Microbiology
Zhou Zhong, Jiying Ning, Emerson A. Boggs, Sooin Jang, Callen Wallace, Cheryl Telmer, Marcel P. Bruchez, Jinwoo Ahn, Alan N. Engelman, Peijun Zhang, Simon C. Watkins, Zandrea Ambrose
Summary: Our study reveals an interaction between CPSF6 and CypA that is crucial for cytoplasmic capsid trafficking and HIV-1 infection. CypA plays a role in preventing premature engagement of HIV-1 capsid with cytoplasmic CPSF6, potentially explaining variations in capsid trafficking and uncoating in different cell types. Understanding these processes can lead to the development of better drugs for preventing HIV infection and pathogenesis.
Article
Virology
Chandra N. Roy, Mariana A. Benitez Moreno, Chris Kline, Zandrea Ambrose
Summary: Developed two viruses encoding a reporter gene that can be expressed in cells after infection. Improved reporter expression reflects HIV-1 replication and showed that two viral variants can be tracked over time in the same animal and can predict failure of antiretroviral therapy to suppress virus. Overall, these viruses can be useful for studying and visualizing HIV-1 infection in humanized mice.
JOURNAL OF VIROLOGY
(2021)
Article
Virology
Hu Zhang, Douglas K. Fischer, Masahiro Shuda, Patrick S. Moore, Shou-Jiang Gao, Zandrea Ambrose, Haitao Guo
Summary: Two SARS-CoV-2 minigenome replicon systems, IVT-CoV2-Rep and BAC-CoV2-Rep, have been developed for research on SARS-CoV-2 virology and antiviral discovery. IVT-CoV2-Rep demonstrates rapid and transient replication in various cell lines, which can be inhibited by known SARS-CoV-2 replication inhibitors. BAC-CoV2-Rep exhibits a stronger and longer replicon signal, and a portion of the signal shows resistance to antiviral treatment.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Review
Virology
Zachary Ingram, Douglas K. Fischer, Zandrea Ambrose
Summary: The study of HIV-1 capsid and its disassembly has been a focus of research over the past decades, revealing its connection to complex replication events and expanding our understanding of its functionality. Various models of capsid disassembly have been proposed, suggesting it may occur in different regions of the cell.
Article
Virology
Kaho H. Tisthammer, Christopher Kline, Tara Rutledge, Collin R. Diedrich, Sergio Ita, Philana Ling Lin, Zandrea Ambrose, Pleuni S. Pennings
Summary: This study evaluated viral diversity in a non-human primate model of SIV-Mtb co-infection and found changes in viral diversity and divergence over 6-9 weeks. Compartmentalization of viral diversity was observed in different tissues, with the highest diversity in thoracic lymph nodes. Viral diversity in lung granulomas was correlated with CD4+ T cell frequency and inversely correlated with CD8+ T cell frequency.
Article
Multidisciplinary Sciences
Shelby Winans, Hyun Jae Yu, Kenia de los Santos, Gary Z. Wang, Vineet N. KewalRamani, Stephen P. Goff
Summary: HIV-1 integration sites are biased towards actively transcribed genes, but a mutation can redirect viral DNA integration to the centromeres of host chromosomes, potentially affecting HIV latency.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Guochao Wei, Naseer Iqbal, Valentine V. Courouble, Ashwanth C. Francis, Parmit K. Singh, Arpa Hudait, Arun S. Annamalai, Stephanie Bester, Szu-Wei Huang, Nikoloz Shkriabai, Lorenzo Briganti, Reed Haney, Vineet N. KewalRamani, Gregory A. Voth, Alan N. Engelman, Gregory B. Melikyan, Patrick R. Griffin, Francisco Asturias, Mamuka Kvaratskhelia
Summary: This study highlights the importance of prion-like low complexity domains in binding and increasing the avidity when interacting with viral capsid, through structural, biochemical, and virological assays.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Guangai Xue, Hyun Jae Yu, Cindy Buffone, Szu-Wei Huang, KyeongEun Lee, Shih Lin Goh, Anna T. T. Gres, Mehmet Hakan Guney, Stefan G. G. Sarafianos, Jeremy Luban, Felipe Diaz-Griffero, Vineet N. N. KewalRamani
Summary: The entry of HIV-1 into the nucleus is regulated by the interaction between the viral capsid protein CA and nuclear pore complex proteins Nup35 and POM121. This interaction is also influenced by soluble host factors such as Cyclophilin A. These findings highlight the role of CA as a macromolecular nuclear transport receptor and provide insights into the mechanism of HIV-1 nuclear invasion.
NATURE COMMUNICATIONS
(2023)
Article
Virology
Richa Dwivedi, Youya Wang, Christopher Kline, Douglas K. Fischer, Zandrea Ambrose
Summary: The V179I substitution in HIV-1 RT is selected during treatment with certain NNRTIs and can enhance drug resistance when present with other resistance mutations. It can arise due to APOBEC-mediated G to A hypermutation and provide a selective advantage for drug-resistant HIV-1 isolates in the presence of some NNRTIs.
FRONTIERS IN VIROLOGY
(2022)