Pathogenesis of cytomegalovirus-associated labyrinthitis in a guinea pig model

Katano, Harutaka; Sato, Yuko; Tsutsui, Yoshihiro; Sata, Tetsutaro; Maeda, Akihiko; Nozawa, Naoki; Inoue, Naoki; Nomura, Yasuya; Kurata, Takeshi

doi:10.1016/j.micinf.2006.11.004

Cited by 51 publications

(33 citation statements)

References 26 publications

(34 reference statements)

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“…15,33 In the MCMV-i.c.-mice, a large number of virus-infected cells were observed in the perilymph and along the CN due to meningogenic expansion, but virus infection did not extend into the endolymph, including CO, as reported previously. 17,29 In the brains of MCMV-i.c.-infected mice, infection spread into the inner ears from the meninges and ventricles, which are connected to the perilymph through the cochlear aqueduct, 33 as reported by Davis and Hawrisiak. 18 It is possible that the endolymph is protected from tympanogenic and meningogenic infection with MCMV by the bloodlabyrinth barrier (BLB).…”

Section: Lps Induce Mcmv-infected Labyrinthitis L Li Et Almentioning

confidence: 85%

“…17 Mock-or MCMV-i.p.-infected mice with i.c. injection of PBS or LPS were used 4 weeks after infection.…”

Section: Auditory Brainstem Responsementioning

confidence: 99%

“…Viral infection was not observed in the scala media (SM) in the endolymph, including the Corti organ (CO) (Figure 3b-e), in accordance with the findings reported previously. 17 However, virus-infected cells were observed in the spiral limbus (SL), including the stria vascularis (SV), in two cases (Figure 3f).…”

Section: Enhancement Of Viral Replication Of the Inner Ear In Mcmv-imentioning

confidence: 99%

“…17 In the present study, we have established an experimental model of hearing loss in mice systemically infected by i.p. inoculation of MCMV into newborn mice.…”

Section: Lps Induce Mcmv-infected Labyrinthitis L Li Et Almentioning

confidence: 99%

“…[13][14][15][16] There was only one report that described the infection of inner ears in fetuses after transplacental infection with GPCMV, in which the infection extended to the perilymph of the inner ears. 17 It was reported that labyrinthitis in the inner ear was induced in newborn mice after intracranial infection with murine CMV (MCMV). 18 However, why the inner ears are so susceptible to CMV infection after congenital CMV infection still remains unclear.…”

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confidence: 99%

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Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection

Kosugi

Han

et al. 2008

Laboratory Investigation

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Congenital cytomegalovirus (CMV) infection is the most common infectious cause of sensorineural hearing loss in children. Here, we established an experimental model of hearing loss after systemic infection with murine CMV (MCMV) in newborn mice. Although almost no viral infection was observed in the inner ears and brains by intraperitoneal (i.p.) infection with MCMV in newborn mice, infection in these regions was induced in combination with intracerebral (i.c.) injection of bacterial lipopolysaccharide (LPS). The susceptibility of the inner ears was higher than that of the brains in terms of viral titer per unit weight. In the labyrinths, the viral infection was associated with the mesenchymal vessels and accompanied by inflammatory cells induced by LPS, causing hematogenous targets of infection in the labyrinths. Viral infection also spread in the perilymph regions such as the scala tympani and scala vestibuli, probably from infected brains via meningogenic and cochlear nerve routes. Viral infection was not observed in the scala media in the endolymph, including the Corti organ. However, viral infection was observed in the spiral limbus, including the stria vascularis. These results suggest that hearing loss caused by labyrinthitis after congenital CMV infection may be enhanced by inflammation caused by systemic bacterial infection in the neonatal period.

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Section: Lps Induce Mcmv-infected Labyrinthitis L Li Et Almentioning

confidence: 85%

“…17 Mock-or MCMV-i.p.-infected mice with i.c. injection of PBS or LPS were used 4 weeks after infection.…”

Section: Auditory Brainstem Responsementioning

confidence: 99%

Section: Enhancement Of Viral Replication Of the Inner Ear In Mcmv-imentioning

confidence: 99%

“…17 In the present study, we have established an experimental model of hearing loss in mice systemically infected by i.p. inoculation of MCMV into newborn mice.…”

Section: Lps Induce Mcmv-infected Labyrinthitis L Li Et Almentioning

confidence: 99%

mentioning

confidence: 99%

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Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection

Kosugi

Han

et al. 2008

Laboratory Investigation

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Viral Diseases

Nomura¹

2013

Morphological Aspects of Inner Ear Disease

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Vaccine Development for Cytomegalovirus

Inoue

Abe

Kobayashi

et al. 2018

Advances in Experimental Medicine and Biology

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The development of a cytomegalovirus (CMV) vaccine has become a top priority due to its potential cost-effectiveness and associated public health benefits. However, there are a number of challenges facing vaccine development including the following: (1) CMV has many mechanisms for evading immune responses , and natural immunity is not perfect, (2) the immune correlates for protection are unclear, (3) a narrow range of CMV hosts limits the value of animal models, and (4) the placenta is a specialized organ formed transiently and its immunological status changes with time. In spite of these limitations, several types of CMV vaccine candidate, including live-attenuated, DISC , subunit, DNA, vectored, and peptide vaccines, have been developed or are currently under development. The recognition of the pentameric complex as the major neutralization target and identification of various strategies to block viral immune response evasion mechanisms have opened new avenues to CMV vaccine development. Here, we discuss the immune correlates for protection, the characteristics of the various vaccine candidates and their clinical trials, and the relevant animal models.

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Pathogenesis of cytomegalovirus-associated labyrinthitis in a guinea pig model

Cited by 51 publications

References 26 publications

Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection

Induction of cytomegalovirus-infected labyrinthitis in newborn mice by lipopolysaccharide: a model for hearing loss in congenital CMV infection

Viral Diseases

Vaccine Development for Cytomegalovirus

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