Cytomegalovirus Infection of Human Lung Epithelial Cells &lt;i&gt;in vitro&lt;/i&gt;

Michelson-Fiske, S; Arnoult, J.; Febvre, H

doi:10.1159/000149933

Cited by 30 publications

(16 citation statements)

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“…2A and data not shown). Several reports have demonstrated syncytium formation by HCMV clinical isolates in fibroblasts and epithelial cells (5,30,42), and the phenotype of the repaired AD169 derivative indicates that the UL131 product is needed for cell-cell fusion. The formation of syncytia would mediate cell-to-cell spread of HCMV while allowing it to evade neutralizing antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the frequent and extensive infection of epithelial cell populations by HCMV in vivo, only a few cultured epithelial cells have been reported to be susceptible to HCMV infection, including primary lung epithelial cells (30), thyroid epithelial cells (26), HCMC and Caco-2 epithelial cells derived from colon (24,40), cervical epithelial cells (41), and BAMB cells derived from amniotic fluid cells (42). However, most analyses of HCMV epithelial cell tropism have been performed using laboratory-adapted strains, and potential variations among virus strains were not taken into consideration.…”

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confidence: 99%

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Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism

Wang

Shenk

2005

J Virol

327

367

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism

Wang

Shenk

2005

J Virol

327

367

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“…In vitro, however, full productive infection is supported only in secondary cell strains of fibroblasts and endothelial cells, in fully differentiated myeloid cells, and in primary cultures of hepatocytes and lung epithelial cells (Michelson-Fiske et al, 1975;Sinzger et al, 1995Sinzger et al, , 1999Plachter et al, 1996). We demonstrated here that human adrenocortical cell lines are fully permissive for infection and replication not only by fibroblast-adapted laboratory HCMV strains but also by clinical isolates of HCMV.…”

Section: Discussionmentioning

confidence: 72%

Human cytomegalovirus productively infects adrenocortical cells and induces an early cortisol response

Trevisan

Matkovič

Cusinato

et al. 2009

Journal Cellular Physiology

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Following our recent findings on the presence of human cytomegalovirus (HCMV) in the normal human adrenal cortex and in adrenocortical tumors, especially in cortisol-secreting tumors, aim of the present study was to investigate the direct effects of HCMV infection on human adrenocortical cells. To this aim, both clinical isolates and laboratory strains of HCMV were used to assess the early effects of infection on human adrenocortical cell morphology, proliferation, gene expression, and steroidogenic function. Both clinical and laboratory HCMV strains could infect and replicate in primary human adrenocortical cell cultures and in adrenocortical carcinoma cell lines, leading to cytopathic changes. Most importantly, in the first hours post-infection (p.i.), adrenocortical cells showed a significant increase of cortisol and estrogen production, paralleled by up-regulation of steroidogenic acute regulatory protein and expression of steroidogenic enzymes involved in the last steps of adrenal steroidogenesis. This effect was probably due to HCMV immediate-early gene expression, since it was most evident in the early phases p.i. and UV-inactivated viral particles did not affect hormone production. Moreover, the effect on steroidogenesis was HCMV specific, since it was not observed after infection with herpes simplex virus. These data suggest that human adrenocortical cells are permissive to HCMV infection and acutely respond to infection with increased cortisol production. An acute glucocorticoid response is typically triggered by infections and is considered to be critical to host defense against pathogens, although, in the case of HCMV infection, it might also enhance viral replication and reactivation from latency.

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“…6E). Given the inherent difficulties in studying virus pathogenesis in human lung, the sole study of HCMV infection in alveolar epithelial cells in vitro was reported more than 3 decades ago (42). Much of our knowledge about the special role of the lung in CMV pathogenesis thus comes from studies of murine CMV (MCMV) infection, where the lung was identified as a major site of MCMV latency and reactivation (4).…”

Section: Discussionmentioning

confidence: 99%

Impaired Surfactant Production by Alveolar Epithelial Cells in a SCID-hu Lung Mouse Model of Congenital Human Cytomegalovirus Infection

Maidji

Kosikova

Joshi

et al. 2012

J Virol

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Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and life-threatening lung-associated diseases in premature infants and immunocompromised children. Although the fetal lung is a major target organ of the virus, HCMV lung pathogenesis has remained unexplored, possibly as a result of extreme host range restriction. To overcome this hurdle, we generated a SCID-hu lung mouse model that closely recapitulates the discrete stages of human lung development in utero. Human fetal lung tissue was implanted into severe combined immunodeficient (CB17-scid) mice and inoculated by direct injection with the VR1814 clinical isolate of HCMV. Virus replication in the fetal lung was assessed by the quantification of infectious virus titers and HCMV genome copies and the detection of HCMV proteins by immunohistochemistry and Western blotting. We show that HCMV efficiently replicated in the lung implants during a 2-week period, forming large viral lesions. The virus productively infected alveolar epithelial and mesenchymal cells, imitating congenital infection of the fetal lung. HCMV replication triggered apoptosis near and within the viral lesions and impaired the production of surfactant proteins in the alveolar epithelium. Our findings highlight that congenital and neonatal HCMV infection can adversely impact lung development, leading to pneumonia and acute lung injury. We have successfully developed a small-animal model that closely recapitulates fetal and neonatal lung development and provides a valuable, biologically relevant tool for an understanding of the lung pathogenesis of HCMV as well as other human respiratory viruses. Additionally, this model would greatly facilitate the development and testing of new antiviral therapies for HCMV along with select human pulmonary pathogens.H uman cytomegalovirus (HCMV) infection of the fetus and premature infants is a major global health problem, and in the United States, HCMV is the leading viral cause of birth defects, affecting about 1% of all live births (16). In congenital infection, HCMV spreads extremely efficiently into fetal organs following fetal viremia. Although pneumonitis is rarely the sole manifestation of congenital HCMV disease in the neonate (62), histological examinations of HCMV-infected fetuses identified the lung as a major target organ, with a large number of HCMV-infected cells (8,25). The main burden of lung-associated HCMV diseases occurs during postnatal infection in premature infants (3,22,34,65) and in immunocompromised children (predominantly after organ or bone marrow transplantation) (27,30,67). Some authors reported high rates (up to 37%) of postnatal cytomegalovirus transmission from seropositive breastfeeding mothers to premature infants (31,41,69). A significant proportion of infected infants develop pneumonitis along with hepatosplenomegaly, lymphadenopathy, enteritis, and aseptic meningitis (12, 36). Although breast milk containing HCMV is not considered dangerous to healthy full-term infants, the risk of development of early...

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Cytomegalovirus Infection of Human Lung Epithelial Cells <i>in vitro</i>

Cited by 30 publications

References 4 publications

Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism

Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism

Human cytomegalovirus productively infects adrenocortical cells and induces an early cortisol response

Impaired Surfactant Production by Alveolar Epithelial Cells in a SCID-hu Lung Mouse Model of Congenital Human Cytomegalovirus Infection

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