Occludin, caveolin‐1, and Alix form a multi‐protein complex and regulate HIV‐1 infection of brain pericytes

Torices, Silvia; Roberts, Samantha; Park, Minseon; Malhotra, Arun; Toborek, Michał

doi:10.1096/fj.202001562r

Cited by 17 publications

(38 citation statements)

References 70 publications

(135 reference statements)

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“…Primary human brain astrocytes, pericytes and human microglia were infected with HIV-1 for 24h and 48h and the expression levels of HIV-1 gag were measured by qPCR. In agreement with previous studies, we found a successful infection of HIV-1 in microglial cells (50,51), pericytes (55)(56)(57), and astrocytes (52)(53)(54). There was signi cantly higher expression of HIV-1 gag 24h after infection compared to 48h in microglia, pericytes, and to a lesser degree in astrocytes (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…EC were excluded from these analyses because no productive HIV-1 infection in EC has been reported (60). The results indicated that astrocytes, pericytes, and microglia are susceptible to HIV-1 infection, con rming literature reports (51,55,56,58). In addition, HIV-1 Gag RNA levels were signi cantly higher 24h after infection when compared to 48h after infection in all three cell types (Fig.…”

Section: Cells Of the Nvu Are Susceptible To Hiv-1 Infectionsupporting

confidence: 80%

“…The CNS is susceptible to infection by lentiviruses, such as HIV-1, through the viral entry from the periphery into the brain (73,88). Several studies have shown that HIV-1 infection modulates gene and protein expression in the host cells (55,87). Therefore, we proposed to evaluate whether HIV-1 infection modulates the expression levels of ACE2 and TMPRSS2.…”

Section: Discussionmentioning

confidence: 99%

“…Brain pericytes express the main HIV-1 receptors, CD4, CCR5 and CXCR4 and can be e ciently infected by HIV-1 (55,59). Therefore, we investigated if HIV-1 infection could lead to alterations of ACE2 or TMPRSS2 expression.…”

Section: No Changes In Ace2 or Tmprss2 Expression Are Detected After mentioning

confidence: 99%

“…In the brain, perivascular macrophages and microglia represent the primary cells infected with HIV (50,51). Several investigations have also shown the capacity of astrocytes to be infected by HIV-1 (52)(53)(54) and recent evidence has emerged on the productive HIV-1 infection of brain pericytes (55)(56)(57)(58)(59). In contrast, no productive HIV-1 infection in EC has been reported (60).…”

Section: Introductionmentioning

confidence: 99%

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Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Torices

Cabrera

Stangis

et al. 2021

Preprint

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Background. Neurological complications are common in patients affected by COVID-19 due to the ability of SARS-CoV-2 to infect brains. While the mechanisms of this process are not fully understood, it has been proposed that SARS-CoV-2 can infect the cells of the neurovascular units (NVU), which form the blood-brain barrier (BBB). The aim of the current study was to analyze the expression pattern of the main SARS-CoV-2 receptors in naïve and HIV-1-infected cells of the NVU in order to elucidate a possible pathway of the virus entry into the brain and a potential modulatory impact of HIV-1 in this process. Methods. The gene and protein expression profile of ACE2, TMPRSS2, ADAM17, BSG, DPP4, AGTR2, ANPEP, cathepsin B and cathepsin L was assessed by qPCR and immunoblotting, respectively. In addition, we investigated if brain endothelial cells can be affected by the exposure to the S1 subunit of the S protein, the domain responsible for the direct binding of SARS-CoV-2 to the ACE2 receptors. Results. The receptors involved in SARS-CoV-2 infection are coexpressed in the cells of the NVU, especially in astrocytes and microglial cells. These receptors are functionally active as exposure of endothelial cells to the SARS CoV-2 S1 protein subunit altered the expression pattern of tight junction proteins, such as claudin-5 and ZO-1. Additionally, HIV-1 infection upregulated ACE2 and TMPRSS2 expression in brain astrocytes and microglia cells.Conclusions. These findings provide key insight into SARS-CoV-2 recognition by cells of the NVU and may help to develop possible treatment of CNS complications of COVID-19.

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Section: Discussionsupporting

confidence: 92%

Section: Cells Of the Nvu Are Susceptible To Hiv-1 Infectionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: No Changes In Ace2 or Tmprss2 Expression Are Detected After mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Torices

Cabrera

Stangis

et al. 2021

Preprint

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Occludin Regulates HIV-1 Infection by Modulation of the Interferon Stimulated OAS Gene Family

et al. 2023

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HIV-1-associated blood brain barrier (BBB) alterations and neurocognitive disorders are frequent clinical manifestations in HIV-1 infected patients. The BBB is formed by cells of the neurovascular unit (NVU) and sealed together by tight junction proteins, such as occludin (ocln). Pericytes are a key cell type of NVU that can harbor HIV-1 infection via a mechanism that is regulated, at least in part, by ocln. After viral infection, the immune system starts the production of interferons, which induce the expression of the 2'-5'-oligoadenylate synthetase (OAS) family of interferon stimulated genes and activate the endoribonuclease RNaseL that provides antiviral protection by viral RNA degradation. The current study evaluated the involvement of the OAS genes in HIV-1 infection of cells of NVU and the role of ocln in controlling OAS antiviral signaling pathway. We identified that ocln modulates the expression levels of the OAS1, OAS2, OAS3, and OASL genes and proteins and, in turn, that the members of the OAS family can influence HIV replication in human brain pericytes. Mechanistically, this effect was regulated via the STAT signaling. HIV-1 infection of pericytes significantly upregulated expression of all OAS genes at the mRNA level but selectively OAS1, OAS2, and OAS3 at the protein level. Interestingly no changes were found in RNaseL after HIV-1 infection. Overall, these results contribute to a better understanding of the molecular mechanisms implicated in the regulation of HIV-1 infection in human brain pericytes and suggest a novel role for ocln in controlling of this process.

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ESCRT machinery and virus infection

Dai,

Feng,

Liao

et al. 2024

Antiviral Research

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Occludin, caveolin‐1, and Alix form a multi‐protein complex and regulate HIV‐1 infection of brain pericytes

Cited by 17 publications

References 70 publications

Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Expression of SARS-CoV-2-related Receptors in Cells of the Neurovascular Unit: Implications for HIV-1 Infection

Occludin Regulates HIV-1 Infection by Modulation of the Interferon Stimulated OAS Gene Family

ESCRT machinery and virus infection

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