Publications by authors named "Kelsie Brooks"

Article Synopsis
  • SARS-CoV-2 not only infects the respiratory system but also causes gastrointestinal (GI) symptoms, leading researchers to study its GI effects in both rhesus macaques and humans.
  • In macaques, infection resulted in viral RNA found in both the respiratory tract and stool, along with decreased levels of certain immune cells in the intestine, suggesting immune disturbance.
  • The study highlighted the translocation of bacteria across the gut barrier during infection and noted that humans recovering from COVID-19 showed decreases in inflammatory markers, indicating a resolution of inflammation linked to GI issues.
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Microbial translocation is a significant contributor to chronic inflammation in people living with HIV (PLWH) and is associated with increased mortality and morbidity in individuals treated for long periods with antiretrovirals. The use of therapeutics to treat microbial translocation has yielded mixed effects, in part, because the species and mechanisms contributing to translocation in HIV remain incompletely characterized. To characterize translocating bacteria, we cultured translocators from chronically SIV-infected rhesus macaques.

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We generated a replication-competent OC43 human seasonal coronavirus (CoV) expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in place of the native spike (rOC43-CoV2 S). This virus is highly attenuated relative to OC43 and SARS-CoV-2 in cultured cells and animals and is classified as a biosafety level 2 (BSL-2) agent by the NIH biosafety committee. Neutralization of rOC43-CoV2 S and SARS-CoV-2 by S-specific monoclonal antibodies and human sera is highly correlated, unlike recombinant vesicular stomatitis virus-CoV2 S.

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Article Synopsis
  • The study investigates how inflammatory responses affect pulmonary disease during SARS-CoV-2 infection, specifically using the rhesus macaque model of mild COVID-19.
  • It highlights the contrasting roles of the cytokines IFNγ and IL-10, where IFNγ contributes to lung lesions but isn't necessary for viral replication suppression, while IL-10 reduces inflammation and aids in T cell memory without hindering viral clearance.
  • The research reveals that IL-10 plays a key role in fostering airway memory T cells, indicating its importance in the immune response during SARS-CoV-2 infection.
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Blockade of the co-inhibitory receptor PD-1 enhances antitumor responses by boosting the function of antigen-specific T cells. Although rare, PD-1 blockade in patients with cancer can lead to exacerbation of infection-associated pathology. Here, we detail the case of a 38-year-old man who was enrolled in a clinical trial for assessment of the safety and activity of anti-PD-1 therapy for Kaposi sarcoma in people with HIV well-controlled on antiretroviral therapy.

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Experimental simian immunodeficiency virus (SIV) infection of Asian macaques is an excellent model for HIV disease progression and therapeutic development. Recent coformulations of nucleoside analogs and an integrase inhibitor have been used for parenteral antiretroviral (ARV) administration in SIV-infected macaques, successfully resulting in undetectable plasma SIV RNA. In a cohort of SIVmac239-infected macaques, we recently observed that administration of coformulated ARVs resulted in an unexpected increase in plasma levels of soluble CD14 (sCD14), associated with stimulation of myeloid cells.

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Article Synopsis
  • The study investigates how two cytokines, IFNγ and IL-10, influence inflammation and immune responses during SARS-CoV-2 infection in rhesus macaques.
  • Blocking IFNγ reduced lung inflammation without significantly affecting immune cell types, whereas blocking IL-10 increased lung inflammation and the presence of virus-specific T cells but hampered their development into specialized cells.
  • Overall, neither cytokine blockade significantly altered the viral load, indicating that these inflammatory pathways play a minimal role in controlling SARS-CoV-2 replication, though IL-10 is important for regulating T cell responses in the lungs.
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The lumen of the gastrointestinal (GI) tract contains an incredibly diverse and extensive collection of microorganisms that can directly stimulate the immune system. There are significant data to demonstrate that the spatial localization of the microbiome can impact viral disease pathogenesis. Here we discuss recent studies that have investigated causes and consequences of GI tract pathologies in HIV, SIV, and SARS-CoV-2 infections with HIV and SIV initiating GI pathology from the basal side and SARS-CoV-2 from the luminal side.

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Defective gastrointestinal barrier function and, in turn, microbial translocation have been identified as significant contributors to persistent inflammation in antiretroviral (ARV)-treated people living with HIV. Metabolic supplementation of short-chain fatty acids (SCFAs), generally produced by the commensal microbiome, may improve these outcomes. Butyrate is a SCFA that is essential for the development and maintenance of intestinal immunity and has a known role in supporting epithelial integrity.

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Article Synopsis
  • SARS-CoV-2 primarily replicates in mucosal sites, and this study used rhesus macaques to investigate the immune responses during mild COVID-19.
  • Viral RNA levels peaked shortly after infection and decreased rapidly, while lung abnormalities and immune cell activation were observed a few days later.
  • T cell responses (CD8 and CD4 T cells) appeared later, indicating that innate immunity may effectively limit the virus's replication before these specific immune cells respond.
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Human immunodeficiency virus (HIV) can persist as an integrated provirus, in a transcriptionally repressed state, within infected cells. This small yet enduring pool of cellular reservoirs that harbor replication-competent HIV is the main barrier to cure. Entry of viral sequences into cellular reservoirs begins shortly after infection, and cells containing integrated proviral DNA are extremely stable once suppressive antiretroviral therapy (ART) is initiated.

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The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the genes to replication capacity.

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The HIV-1 reservoir consists of latently infected cells that persist despite antiretroviral therapy (ART). Elucidating the proviral genetic composition of the reservoir, particularly in the context of pre-therapy viral diversity, is therefore important to understanding reservoir formation and the persistence of latently infected cells. Here we investigate reservoir proviral variants from 13 Zambian acutely-infected individuals with additional pre-therapy sampling for a unique comparison to the ART-naïve quasispecies.

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The influence of biological sex on disease progression in HIV-1-infected individuals has been focused on the chronic stage of infection, but little is known about how sex differences influence acute HIV-1 infection. We observed profound differences in viral load and CD4 T cell activation from the earliest time points in men and women in a Zambian heterosexual acute infection cohort. Women exhibited a >2-fold higher rate of CD4 T cell loss despite significantly lower viral loads (VL) than men.

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Understanding the impact of concussion history on mental health-mood disorders and substance use-is an essential step in characterizing the psychological and behavioral consequences of concussion and in developing effective treatments. The objective of this study was to examine the association between the history of concussion and substance abuse by investigating both its direct and indirect association via mood disorder. A secondary objective was to determine whether gender moderates the association.

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Unlabelled: There are two subgroups of respiratory syncytial virus (RSV), A and B, and within each subgroup, isolates are further divided into clades. Several years ago, multiple subgroup B isolates which contained a duplication of 60 nucleotides in the glycoprotein (G) gene were described. These isolates were given a new clade designation of BA based on the site of isolation, Buenos Aires, Argentina.

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HIV-1 infection is characterized by varying degrees of chronic immune activation and disruption of T-cell homeostasis, which impact the rate of disease progression. A deeper understanding of the factors that influence HIV-1-induced immunopathology and subsequent CD4(+) T-cell decline is critical to strategies aimed at controlling or eliminating the virus. In an analysis of 127 acutely infected Zambians, we demonstrate a dramatic and early impact of viral replicative capacity (vRC) on HIV-1 immunopathogenesis that is independent of viral load (VL).

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