Cytomegalovirus infection of the nasopharynx

Chan, Bik Wan Amy

doi:10.1136/jcp.55.12.970

Cited by 14 publications

(6 citation statements)

References 3 publications

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“…Recent work showed that natural MCMV transmission from infected mothers to pups occurs through the nasal mucosa [5]. Moreover, human CMV is thought to infect via an oral/nasal route [6][7][8][9][10][11] and it has been proposed that the nasal mucosa may be the dominant site of entry [5]. Very little is known about the immune response or viral dissemination after a nasal infection.…”

Section: Discussionmentioning

confidence: 99%

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Hematopoietic cell-mediated dissemination of murine cytomegalovirus is regulated by NK cells and immune evasion

et al. 2021

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Cytomegalovirus (CMV) causes clinically important diseases in immune compromised and immune immature individuals. Based largely on work in the mouse model of murine (M)CMV, there is a consensus that myeloid cells are important for disseminating CMV from the site of infection. In theory, such dissemination should expose CMV to cell-mediated immunity and thus necessitate evasion of T cells and NK cells. However, this hypothesis remains untested. We constructed a recombinant MCMV encoding target sites for the hematopoietic specific miRNA miR-142-3p in the essential viral gene IE3. This virus disseminated poorly to the salivary gland following intranasal or footpad infections but not following intraperitoneal infection in C57BL/6 mice, demonstrating that dissemination by hematopoietic cells is essential for specific routes of infection. Remarkably, depletion of NK cells or T cells restored dissemination of this virus in C57BL/6 mice after intranasal infection, while dissemination occurred normally in BALB/c mice, which lack strong NK cell control of MCMV. These data show that cell-mediated immunity is responsible for restricting MCMV to hematopoietic cell-mediated dissemination. Infected hematopoietic cells avoided cell-mediated immunity via three immune evasion genes that modulate class I MHC and NKG2D ligands (m04, m06 and m152). MCMV lacking these 3 genes spread poorly to the salivary gland unless NK cells were depleted, but also failed to replicate persistently in either the nasal mucosa or salivary gland unless CD8+ T cells were depleted. Surprisingly, CD8+ T cells primed after intranasal infection required CD4+ T cell help to expand and become functional. Together, our data suggest that MCMV can use both hematopoietic cell-dependent and -independent means of dissemination after intranasal infection and that cell mediated immune responses restrict dissemination to infected hematopoietic cells, which are protected from NK cells during dissemination by viral immune evasion. In contrast, viral replication within mucosal tissues depends on evasion of T cells.

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Section: Discussionmentioning

confidence: 99%

“…Recent work has identified the nasal mucosa of mice as a potential natural site of primary MCMV infection [5]. The oral/nasal mucosa is also a likely site of entry in humans [6][7][8][9][10][11], making it an important area for investigation. After entry, CMV must disseminate to sites of shedding including the salivary gland and kidney.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic cell-mediated dissemination of murine cytomegalovirus is regulated by NK cells and immune evasion

et al. 2021

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“…Based on similar characteristics of human and murine CMVs, we hypothesize that the nasal mucosa might also be a target organ for HCMV. In line with this, there have been several reports on the detection of HCMV in nasopharyngeal carcinomas, sinusitis and nasal polyposis [ 34 - 37 ]. In lungs, both strains showed a very restricted replication during the first three weeks after post inoculation, after which the infection was controlled.…”

Section: Discussionmentioning

confidence: 66%

Comparison of the pathogenesis of the highly passaged MCMV Smith strain with that of the low passaged MCMV HaNa1 isolate in BALB/c mice upon oronasal inoculation

Zhang

Xiang

Doorsselaere

et al. 2015

Vet Res

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Murine cytomegalovirus (MCMV) Smith strain is widely used in mouse models to study HCMV infections. Due to high serial passages, MCMV Smith has acquired genetic and biological changes. Therefore, a low passaged strain would be more relevant to develop mouse models. Here, the pathogenesis of an infection with MCMV Smith was compared with that of an infection with a low passaged Belgian MCMV isolate HaNa1 in BALB/c adult mice following oronasal inoculation with either a low (104 TCID50/mouse) or high (106 TCID50/mouse) inoculation dose. Both strains were mainly replicating in nasal mucosa and submandibular glands for one to two months. In nasal mucosa, MCMV was detected earlier and longer (1–49 days post inoculation (dpi)) and reached higher titers with the high inoculation dose compared to the low inoculation dose (14–35 dpi). In submandibular glands, a similar finding was observed (high dose: 7–49 dpi; low dose: 14–42 dpi). In lungs, both strains showed a restricted replication. In spleen, liver and kidneys, only the Smith strain established a productive infection. The infected cells were identified as olfactory neurons and sustentacular cells in olfactory epithelium, macrophages and dendritic cells in NALT, acinar cells in submandibular glands, and macrophages and epithelial cells in lungs for both strains. Antibody analysis demonstrated for both strains that IgG2a was the main detectable antibody subclass. Overall, our results show that significant phenotypic differences exist between the two strains. MCMV HaNa1 has been shown to be interesting for use in mouse models in order to get better insights for HCMV infections in immunocompetent humans.

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“…In a previous study by [25,26] also detected HCMV nucleic acids predominantly in the nuclear localization of the cancerous tissues. Moreover, nuclear integration HCMV-DNA of tumor tissues was regarded as an early event in the mutagenic process of their involvement associated with viral promotion of DNA damage and/or tumor initiation [27,28].…”

Section: Discussionmentioning

confidence: 77%

Localization of Herpetic Viruses Patterns in Sinonasal and Nasopharyngeal Malignant and Benign Tumors

Mahmood

2019

OJOR

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Cytomegalovirus infection of the nasopharynx

Cited by 14 publications

References 3 publications

Hematopoietic cell-mediated dissemination of murine cytomegalovirus is regulated by NK cells and immune evasion

Hematopoietic cell-mediated dissemination of murine cytomegalovirus is regulated by NK cells and immune evasion

Comparison of the pathogenesis of the highly passaged MCMV Smith strain with that of the low passaged MCMV HaNa1 isolate in BALB/c mice upon oronasal inoculation

Localization of Herpetic Viruses Patterns in Sinonasal and Nasopharyngeal Malignant and Benign Tumors

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