Growth of Measles Virus in Epithelial and Lymphoid Tissues of Cynomolgus Monkeys

Sakaguchi, Masahiro; Yoshikawa, Yasuhiro; Yamanouchi, Kazuya; Sata, Tetsutaro; Nagashima, Kazuo; Takeda, Keisuke

doi:10.1111/j.1348-0421.1986.tb03036.x

Cited by 48 publications

(37 citation statements)

References 10 publications

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“…Infection of tissue lymphocytes during acute measles has been documented but not quantified (34)(35)(36). Up to 5% infected PBMCs were detected in one measles patient from whom blood was obtained 3 days after rash appearance, and much lower levels were detected in patients from whom blood was obtained a few days later (35).…”

Section: Discussionmentioning

confidence: 99%

Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

Messling

Milošević

Cattaneo

2004

Proc. Natl. Acad. Sci. U.S.A.

179

200

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The immunosuppressive properties of morbilliviruses including measles and canine distemper virus (CDV) are well known, but the host cells supporting infection are poorly characterized. To identify these cells, a recombinant CDV expressing green fluorescent protein was produced by reverse genetics based on a wild-type strain lethal for ferrets. This recombinant virus fully retained virulence and blazed three lymphocyte-based pathways through the immune system of its host: first, it infected rapidly and massively circulating B and T cells; second, it took over and damaged secondary lymphatic organs including spleen, lymph nodes, and gut-associated and mucosal lymphoid tissues; third, it infected most thymocytes. In contrast, replication in epithelial cells was initially not detectable, but substantial before host death. Thus, CDV initially infects lymphocytes and massively replicates therein, thereby causing immunosuppression and preparing systemic invasion and host escape.virus ͉ measles ͉ immunosuppression

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Section: Discussionmentioning

confidence: 99%

Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

Messling

Milošević

Cattaneo

2004

Proc. Natl. Acad. Sci. U.S.A.

179

200

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“…Fever, cough, conjunctivitis, and the appearance of a generalized rash characterize this highly contagious disease (12). The primary infection with MV begins in the respiratory tract; specifically, studies of experimentally infected primates and human autopsy tissue show virus propagation in tracheal and bronchial epithelial cells (22). Initiation of infection occurs more readily in the conducting airways than in the nasopharynx (10).…”

Section: Measles Virus (Mv) Exemplifies the Morbillivirus Genus In Thementioning

confidence: 99%

Measles Virus Preferentially Transduces the Basolateral Surface of Well-Differentiated Human Airway Epithelia

Sinn

Williams

Vongpunsawad

et al. 2002

J Virol

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Measles virus (MV) is typically spread by aerosol droplets and enters via the respiratory tract. The progression of MV infection has been widely studied; yet, the pathway for virus entry in polarized human airway epithelia has not been investigated. Herein we report the use of a replication-competent Edmonston vaccine strain of MV expressing enhanced green fluorescent protein (MV-eGFP) to infect primary cultures of well-differentiated human airway epithelia. Previous studies with polarized Caco-2 cells (intestine-derived human epithelia) and MDCK cells (kidney-derived canine epithelia) demonstrated that MV primarily infected and exited the apical surface. In striking contrast, our results indicate that MV preferentially transduces human airway cells from the basolateral surface; however, virus release remains in an apical direction. When MV-eGFP was applied apically or basolaterally to primary cultures of airway epithelia, discrete foci of eGFP expression appeared and grew; however, the cell layer integrity was maintained for the duration of the study (7 days). Interestingly, utilizing immunohistochemistry and confocal microscopy, we observed widespread expression of the receptor for the vaccine strain of MV (CD46) at greatest abundance on the apical surface of the differentiated human airway epithelia as well as in human tracheal tissue sections. These data suggest that the progression of MV infection through the respiratory epithelium may involve pathways other than direct binding and entry through the apical surface of airway epithelia.

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“…It is currently thought that MV, a member of the Morbillivirus genus of the Paramyxoviridae family, infects the upper respiratory epithelium from the luminal side before spreading in lymphatic cells (2,3). It is undisputed that eventually, MV infection can spread to many organs including the respiratory tract (4)(5)(6). However, no direct evidence exists for primary MV replication in respiratory epithelial cells, whereas rapid and massive spread of morbillivirus infection through lymphatic cells expressing the signaling lymphocytic activation molecule (SLAM; CD150) (7) was recently documented (8).…”

Section: Introductionmentioning

confidence: 99%

Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed

et al. 2008

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The current model of measles virus (MV) pathogenesis implies that apical infection of airway epithelial cells precedes systemic spread. An alternative model suggests that primarily infected lymphatic cells carry MV to the basolateral surface of epithelial cells, supporting MV shedding into the airway lumen and contagion. This model predicts that a mutant MV, unable to enter cells through the unidentified epithelial cell receptor (EpR), would remain virulent but not be shed. To test this model, we identified residues of the MV attachment protein sustaining EpR-mediated cell fusion. These nonpolar or uncharged polar residues defined an area located near the binding site of the signaling lymphocytic activation molecule (SLAM), the receptor for MV on lymphatic cells. We then generated an EpR-blind virus maintaining SLAM-dependent cell entry and inoculated rhesus monkeys intranasally. Hosts infected with the selectively EpR-blind MV developed rash and anorexia while averaging slightly lower viremia than hosts infected with wild-type MV but did not shed virus in the airways. The mechanism restricting shedding was characterized using primary well-differentiated human airway epithelial cells. Wild-type MV infected columnar epithelial cells bearing tight junctions only when applied basolaterally, while the EpR-blind virus did not infect these cells. Thus, EpR is probably a basolateral protein, and infection of the airway epithelium is not essential for systemic spread and virulence of MV.

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Growth of Measles Virus in Epithelial and Lymphoid Tissues of Cynomolgus Monkeys

Cited by 48 publications

References 10 publications

Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

Tropism illuminated: Lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system

Measles Virus Preferentially Transduces the Basolateral Surface of Well-Differentiated Human Airway Epithelia

Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed

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