HIV internalization into oral and genital epithelial cells by endocytosis and macropinocytosis leads to viral sequestration in the vesicles

Yasen, Aizezi; Herrera, Rossana; Rosbe, Kristina W.; Lien, Kathy; Tugizov, Sharof M.

doi:10.1016/j.virol.2017.12.012

Cited by 33 publications

(59 citation statements)

References 128 publications

(212 reference statements)

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“…Fungal invasins derived from Candida albicans stimulated epidermal growth factor receptor which caused rearrangement of the epithelial microfilaments and the formation of pseudopods taking up the fungus into the epithelial cells. In case of HIV, several pathways such as clathrin-, caveolin/lipid raft-associated endocytosis and micropinocytosis were involved in the epithelial uptake of the virus 38,39,40 The transferrin receptor (TfR) is another receptor relevant for endocytosis at the oral epithelium. TfR was used as a marker for oral epithelial cells and was reported to mediate the uptake of Porphyromonas gingivalis, a well-known periodontal pathogen.…”

Section: Endocytosismentioning

confidence: 99%

Cell culture models of oral mucosal barriers: A review with a focus on applications, culture conditions and barrier properties

et al. 2018

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Understanding the function of oral mucosal epithelial barriers is essential for a plethora of research fields such as tumor biology, inflammation and infection diseases, microbiomics, pharmacology, drug delivery, dental and biomarker research. The barrier properties are comprised by a physical, a transport and a metabolic barrier, and all these barrier components play pivotal roles in the communication between saliva and blood. The sum of all epithelia of the oral cavity and salivary glands is defined as the blood-saliva barrier. The functionality of the barrier is regulated by its microenvironment and often altered during diseases. A huge array of cell culture models have been developed to mimic specific parts of the blood-saliva barrier, but no ultimate standard in vitro models have been established. This review provides a comprehensive overview about developed in vitro models of oral mucosal barriers, their applications, various cultivation protocols and corresponding barrier properties.

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Section: Endocytosismentioning

confidence: 99%

Cell culture models of oral mucosal barriers: A review with a focus on applications, culture conditions and barrier properties

et al. 2018

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“…Axl is expressed on human primary endothelial cells [27]. TIM-1 is expressed on human epithelial cells and mediated HIV-1 binding to the cells [66]. These cells do not express CD4 and therefore cannot be infected by HIV-1 according to our data summarized in Fig.…”

Section: The Roles Of Hiv-1 Envelope Ptdser In Virus Binding and Entrymentioning

confidence: 89%

Roles of phosphatidylserine exposed on the viral envelope and cell membrane in HIV-1 replication

et al. 2019

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Phosphatidylserine (PtdSer) is usually present only in the inner leaf of the lipid bilayers of the cell membrane, but is exposed on the outer leaf when cells are activated and/or die. Exposure of PtdSer has physiological functions. For example, the PtdSer exposed on dead cells can serve as “eat-me signals” for phagocytes to clear dead cells by phagocytosis, which prevents autoimmune reactions and inflammation. HIV-1 induces PtdSer exposure on infected and target cells and it also exposes PtdSer on its envelope. Recent studies showed that PtdSer exposed on the HIV-1 envelope and infected and target cells can facilitate or inhibit multiple steps of HIV-1 replication.At the virus binding and entry steps, interaction of the envelope PtdSer and the host’s PtdSer-binding molecules can enhance HIV-1 infection of cells by facilitating virus attachment. At the virus budding step, HIV-1 can be trapped on the cell surface by one family of PtdSer-binding receptors, T-cell immunoglobulin mucin domain proteins (TIM)-1, 3, and 4 expressed on virus producer cells. Although this trapping can inhibit release of HIV-1, one of the HIV-1 accessory gene products, Negative Factor (Nef), can counteract virus trapping by TIM family receptors (TIMs) by inducing the internalization of these receptors. HIV-1 infection can induce exposure of PtdSer on infected cells by inducing cell death. A soluble PtdSer-binding protein in serum, protein S, bridges PtdSer exposed on HIV-1-infected cells and a receptor tyrosine kinase, Mer, expressed on macrophages and mediate phagocytic clearance of HIV-1 infected cells. HIV-1 can also induce exposure of PtdSer on target cells at the virus binding step. Binding of HIV-1 envelope proteins to its receptor (CD4) and co-receptors (CXCR4 or CCR5) elicit signals that induce PtdSer exposure on target cells by activating TMEM16F, a phospholipid scramblase. PtdSer exposed on target cells enhances HIV-1 infection by facilitating fusion between the viral envelope and target cell membrane. Because various other phospholipid channels mediating PtdSer exposure have recently been identified, it will be of interest to examine how HIV-1 actively interacts with these molecules to manipulate PtdSer exposure levels on cells and viral envelope to support its replication.

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“…Following attachment of HIV‐1 to epithelial cells containing CD4‐alternate receptors, HSPGs and GC, the whole virions are endocytosed and transcytosed into the stromal layer, so that they can productively infect leukocytes present in this area . However, it has been shown in HT‐29 epithelial cells that the GC‐gp120 interaction facilitates subsequent binding of gp120 and gp41 to CXCR4, which is co‐expressed with and localized adjacently to GC .…”

Section: Discussionmentioning

confidence: 99%

Sperm can act as vectors for HIV‐1 transmission into vaginal and cervical epithelial cells

Young

Tatieng

Kongmanas

et al. 2019

American J Rep Immunol

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Problem Sperm are the major cells in semen. Human sperm possess a number of HIV‐1 gp120 binding ligands including sulfogalactosylglycerolipid (SGG). However, the mechanisms of how sperm capture HIV‐1 onto their surface are unclear. Furthermore, the ability of sperm to deliver HIV‐1 to vaginal/cervical epithelial cells lining the lower female reproductive tract, as a first step in HIV‐1 transmission, needs to be determined. Method of study Sperm from healthy donors were incubated with dual‐tropic HIV‐1CS204 (clinical isolate), and virus capture was determined by p24 antigen ELISA. The involvement of SGG in HIV‐1 capture was assessed by determining Kd values of HIV‐1 gp120‐SGG binding as well as computational docking of SGG to the gp120 V3 loop. The ability of sperm‐associated HIV‐1 to infect peripheral blood mononuclear cells (PBMCs) and TZM‐bl indicator cells was determined. Lastly, infection of vaginal (Vk2/E6E7), ectocervical (Ect1/E6E7), and endocervical (End1/E6E7) epithelial cells mediated by HIV‐1–associated sperm was evaluated. Results Sperm were able to capture HIV‐1 in a dose‐dependent manner, and the capture reached a maximum within 5 minutes. Captured HIV‐1, however, could be removed from sperm by Percoll‐gradient centrifugation. Affinity of gp120 for SGG was substantial, implicating sperm SGG in HIV‐1 capture. Sperm‐associated HIV‐1 could productively infect PBMCs and TZM‐bl cells, and was capable of being transmitted into vaginal/cervical epithelial cells. Conclusion Sperm are able to capture HIV‐1, which remains infectious and is able to be transmitted into vaginal/cervical epithelial cells, a result indicating the importance of sperm in HIV transmission.

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HIV internalization into oral and genital epithelial cells by endocytosis and macropinocytosis leads to viral sequestration in the vesicles

Cited by 33 publications

References 128 publications

Cell culture models of oral mucosal barriers: A review with a focus on applications, culture conditions and barrier properties

Cell culture models of oral mucosal barriers: A review with a focus on applications, culture conditions and barrier properties

Roles of phosphatidylserine exposed on the viral envelope and cell membrane in HIV-1 replication

Sperm can act as vectors for HIV‐1 transmission into vaginal and cervical epithelial cells

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