Adenovirus Infections in the Immunocompromised Host

Krilov, Leonard R.

doi:10.1097/01.inf.0000165306.95815.68

Cited by 30 publications

(19 citation statements)

References 14 publications

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“…Monolayers were cultured on 12-well cell culture inserts as described above and treated with control (PBS), CM, CXCL8 or CM preincubated with anti-CXCL8 neutralizing antibodies for 4 h. Cells were fixed with 3% paraformaldehyde (PFA), quenched with 25 mM NH 4 Cl and permeabilized with 0.5% Triton X-100. Filters were quartered and incubated with the first antibody at 4 °C overnight.…”

Section: Methodsmentioning

confidence: 99%

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

et al. 2011

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mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανβ3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells.

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Section: Methodsmentioning

confidence: 99%

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

et al. 2011

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“…Feng He, 1, † sangeeta B. Joshi, 1 David s. Moore, 2 Heather e. shinogle, 2 satoshi Ohtake, 3 David Lechuga-Ballesteros,…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4] Since the first documented Ad breakout among military recruits, 5 51 serotypes of adenoviruses have been identified using antisera neutralization methods. 6,7 Adenovirus is a nonenveloped virus containing a linear, doublestranded DNA (~13% of its mass).…”

Section: Introductionmentioning

confidence: 99%

“…In this study, multiple spectroscopic techniques together with transmission electron microscopy (TeM) were employed to probe viral stability and to improve pharmaceutical formulations of ad4-based vaccines and DNa carriers. perturbations of secondary, tertiary and quaternary structure of ad4 proteins induced by elevated temperatures over a wide pH range (3)(4)(5)(6)(7)(8) were analyzed using circular dichroism, UV absorption and intrinsic and extrinsic fluorescence spectroscopy as well as static and dynamic light scattering. The spectroscopic results obtained indicate a decrease in ad4 stability as pH increases from 4 to 8, similar to the behavior reported previously for ad2 and ad5, although the ad4 virion appears to possess slightly more tolerance to thermal stress.…”

Section: Introductionmentioning

confidence: 99%

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Using spectroscopic and microscopic methods to probe the structural stability of human adenovirus type 4

He¹,

Joshi²,

Moore³

et al. 2010

Human Vaccines

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“…More than one-third of HAdVs are associated with disease in the respiratory, digestive, excretory, and ocular systems (44,55,71). Fatal cases of HAdV infections were reported from immunosuppressed patients due to T-lymphocyte deficiencies (52), while infections in immunocompetent individuals are usually self limiting.…”

mentioning

confidence: 99%

Cell-Free Transmission of Human Adenovirus by Passive Mass Transfer in Cell Culture Simulated in a Computer Model

Yakimovich

Gumpert

Burckhardt

et al. 2012

J Virol

130

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Viruses spread between cells, tissues, and organisms by cell-free and cell-cell transmissions. Both mechanisms enhance disease development, but it is difficult to distinguish between them. Here, we analyzed the transmission mode of human adenovirus (HAdV) in monolayers of epithelial cells by wet laboratory experimentation and a computer simulation. Using live-cell fluorescence microscopy and replication-competent HAdV2 expressing green fluorescent protein, we found that the spread of infection invariably occurred after cell lysis. It was affected by convection and blocked by neutralizing antibodies but was independent of second-round infections. If cells were overlaid with agarose, convection was blocked and round plaques developed around lytic infected cells. Infected cells that did not lyse did not give rise to plaques, highlighting the importance of cell-free transmission. Key parameters for cell-free virus transmission were the time from infection to lysis, the dose of free viruses determining infection probability, and the diffusion of single HAdV particles in aqueous medium. With these parameters, we developed anin silicomodel using multiscale hybrid dynamics, cellular automata, and particle strength exchange. This so-called white box model is based on experimentally determined parameters and reproduces viral infection spreading as a function of the local concentration of free viruses. These analyses imply that the extent of lytic infections can be determined by either direct plaque assays or can be predicted by calculations of virus diffusion constants and modeling.

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Adenovirus Infections in the Immunocompromised Host

Cited by 30 publications

References 14 publications

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

Using spectroscopic and microscopic methods to probe the structural stability of human adenovirus type 4

Cell-Free Transmission of Human Adenovirus by Passive Mass Transfer in Cell Culture Simulated in a Computer Model

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