Dynamic Virus-Bacterium Interactions in a Porcine Precision-Cut Lung Slice Coinfection Model: Swine Influenza Virus Paves the Way for Streptococcus suis Infection in a Two-Step Process

Meng, Fanxiang; Wu, Nai Huei; Nerlich, Andreas; Herrler, Georg; Valentin‐Weigand, Peter; Seitz, Maren

doi:10.1128/iai.00171-15

Cited by 62 publications

(103 citation statements)

References 46 publications

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“…This result is most likely due to the presence of sialic acid on the capsular polysaccharide of wt strain 10 and the 10Δsly mutant. Recent studies have shown that the sialic acid binding activities of influenza viruses recognize the capsular sialic acid of S. suis, resulting in bacterial adherence to influenza virus-infected cells (6,10,19,20). The 10Δsly mutant is encapsulated and, therefore, can benefit from this adherence mechanism, too.…”

Section: Resultsmentioning

confidence: 99%

“…Influenza virus infections may cause increased susceptibility to secondary bacterial pneumonia, resulting in increased morbidity and mortality rates in the human population; the mechanisms underlying this copathogenesis are not well understood (13,14). For S. suis, it has been shown that the interaction of influenza A virus hemagglutinins with capsular sialic acids results in the binding of streptococci to virus-infected cells (6,19,20). This adherence mechanism is more efficient than the binding mediated by bacterial adhesins (6,10).…”

Section: Discussionmentioning

confidence: 99%

“…Coinfections with influenza viruses may affect the course of Streptococcus suis infections, as has been shown recently in a precision-cut lung slice model and in immortalized cells (6,19,20). S. suis is an important bacterial pathogen causing a number of infectious disease syndromes in pigs worldwide, including arthritis, septicemia, meningitis, and pneumonia (21,22), and it has been described to be an emerging zoonotic pathogen posing a potential risk for global public health (21,23).…”

mentioning

confidence: 90%

“…Coinfections of the respiratory tract by viruses and bacteria are a common clinical manifestation (3,4). Numerous studies have investigated the complications of viral infections and how they increase susceptibility to and morbidity from secondary bacterial infections, for example, by disrupting epithelial barriers (5,6), modulating immune responses and inflammatory reactions (7,8), or increasing bacterial attachment or colonization (9,10). During the 1918 influenza pandemic, thousands of fatal cases were due to secondary bacterial pneumonia, particularly pneumonia caused by Streptococcus pneumoniae (11).…”

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confidence: 99%

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Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

et al. 2019

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Streptococcus suis is an important zoonotic pathogen which can infect humans and pigs worldwide, posing a potential risk to global public health. Suilysin, a pore-forming cholesterol-dependent cytolysin, is considered to play an important role in the pathogenesis of S. suis infections. It is known that infection with influenza A viruses may favor susceptibility to secondary bacterial infection, resulting in more severe disease and increased mortality. However, the molecular mechanisms underlying these coinfections are incompletely understood. Applying highly differentiated primary porcine respiratory epithelial cells grown under air-liquid interface (ALI) conditions, we analyzed the contribution of swine influenza viruses (SIV) to the virulence of S. suis, with a special focus on its cytolytic toxin, suilysin. We found that during secondary bacterial infection, suilysin of S. suis contributed to the damage of well-differentiated respiratory epithelial cells in the early stage of infection, whereas the cytotoxic effects induced by SIV became prominent at later stages of infection. Prior infection by SIV enhanced the adherence to and colonization of porcine airway epithelial cells by a wild-type (wt) S. suis strain and a suilysin-negative S. suis mutant in a sialic acid-dependent manner. A striking difference was observed with respect to bacterial invasion. After bacterial monoinfection, only the wt S. suis strain showed an invasive phenotype, whereas the mutant remained adherent. When the epithelial cells were preinfected with SIV, the suilysin-negative mutant also showed an invasion capacity. Therefore, we propose that coinfection with SIV may compensate for the lack of suilysin in the adherence and invasion process of suilysin-negative S. suis. FIG 4Invasion of the bronchiolar epithelium by S. suis after preinfection with SIV. PBEC were preinfected with 5 ϫ 10 4 TCID 50 /filter H3N2 for 24 h, subsequently inoculated with S. suis wt strain 10 or the 10Δsly mutant at 2.5 ϫ 10 7 /filter from the apical compartment for 4 h, and then washed thoroughly to remove nonadherent bacteria and further incubated under ALI conditions until 48 hpi. Before fixation, the infected cells were washed with PBS to remove nonadherent bacteria. PBEC monoinfected with S. suis wt strain 10, the 10Δsly mutant, or H3N2 and mock-infected cells served as controls. (A) Immunostaining detection for colocalization of streptococci with H3N2-infected cells in the bronchiolar epithelium. Streptococci are labeled in green, nucleoproteins of H3N2 are stained in red, and nuclei are shown in blue (DAPI). The areas in the squares in the center of the panels in the bottom row are magnified in the insets at the top left of those panels. Bars, 25 m. (B) Immunostaining detection for invasion of streptococci into the bronchiolar epithelium, with vertical sections of PBEC being shown. Streptococci are labeled in green, nucleoproteins of H3N2 are stained in red, and nuclei are shown in blue (DAPI). White arrows indicate tissue-invasive bacteria, and the dashed...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

et al. 2019

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“…Finally, all of the samples were stored at 4°C until examination under a Nikon Eclipse Ti-S inverse immunofluorescence microscope equipped with a 10ϫ/0.30 Plan Fluor objective (Nikon). Subsequently, the area of the NPTr cells surface positive for red fluorescent HA protein was analyzed by applying analySIS 3.2 software (Soft Imaging System) to quantify HA attachment (73).…”

Section: Methodsmentioning

confidence: 99%

Mutations during the Adaptation of H9N2 Avian Influenza Virus to the Respiratory Epithelium of Pigs Enhance Sialic Acid Binding Activity and Virulence in Mice

Yang

Punyadarsaniya

Lambertz

et al. 2017

J Virol

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The natural reservoir for influenza viruses is waterfowl, and from there they succeeded in crossing the barrier to different mammalian species. We analyzed the adaptation of avian influenza viruses to a mammalian host by passaging an H9N2 strain three times in differentiated swine airway epithelial cells. Using precisioncut slices from the porcine lung to passage the parental virus, isolates from each of the three passages (P1 to P3) were characterized by assessing growth curves and ciliostatic effects. The only difference noted was an increased growth kinetics of the P3 virus. Sequence analysis revealed four mutations: one each in the PB2 and NS1 proteins and two in the HA protein. The HA mutations, A190V and T212I, were characterized by generating recombinant viruses containing either one or both amino acid exchanges. Whereas the parental virus recognized ␣2,3-linked sialic acids preferentially, the HA190 mutant bound to a broad spectrum of glycans with ␣2,6/8/9-linked sialic acids. The HA212 mutant alone differed only slightly from the parental virus; however, the combination of both mutations (HA190ϩHA212) increased the binding affinity to those glycans recognized by the HA190 mutant. Remarkably, only the HA double mutant showed a significantly increased pathogenicity in mice. In contrast, none of those mutations affected the ciliary activity of the epithelial cells which is characteristic for virulent swine influenza viruses. Taken together, our results indicate that shifts in the HA receptor affinity are just an early adaptation step of avian H9N2 strains; further mutational changes may be required to become virulent for pigs.IMPORTANCE Swine play an important role in the interspecies transmission of influenza viruses. Avian influenza A viruses (IAV) of the H9N2 subtype have successfully infected hosts from different species but have not established a stable lineage. We have analyzed the adaptation of IAV-H9N2 virus to target cells of a new host by passaging the virus three times in differentiated porcine respiratory epithelial cells. Among the four mutations detected, the two HA mutations were analyzed by generating recombinant viruses. Depending on the infection system used, the mutations differed in their phenotypic expression, e.g., sialic acid binding activity, replication kinetics, plaque size, and pathogenicity in inbred mice. However, none of the mutations affected the ciliary activity which serves as a virulence marker. Thus, early

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Initial steps of the pathogenesis of the infection caused byStreptococcus suis: fighting against nonspecific defenses

et al. 2016

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Edited by Wilhelm JustInteractions between a bacterial pathogen and its potentially susceptible host are initiated with the colonization step. During respiratory/oral infection, the pathogens must compete with the normal microflora, resist defense mechanisms of the local mucosal immunity, and finally reach, adhere, and breach the mucosal epithelial cell barrier in order to induce invasive disease. This is the case during infection by the swine and zoonotic pathogen Streptococcus suis, which is able to counteract mucosal barriers to induce severe meningitis and sepsis in swine and in humans. The initial steps of the pathogenesis of S. suis infection has been a neglected area of research, overshadowed by studies on the systemic and central nervous phases of the disease. In this Review article, we provide for the first time, an exclusive focus on S. suis colonization and the potential mechanisms involved in S. suis establishment at the mucosa, as well as the mechanisms regulating mucosal barrier breakdown. The role of mucosal immunity is also addressed. Finally, we demystify the extensive list of putative adhesins and virulence factors reported to be involved in the initial steps of pathogenesis by S. suis.

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Dynamic Virus-Bacterium Interactions in a Porcine Precision-Cut Lung Slice Coinfection Model: Swine Influenza Virus Paves the Way for Streptococcus suis Infection in a Two-Step Process

Cited by 62 publications

References 46 publications

Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

Viral Coinfection Replaces Effects of Suilysin on Streptococcus suis Adherence to and Invasion of Respiratory Epithelial Cells Grown under Air-Liquid Interface Conditions

Mutations during the Adaptation of H9N2 Avian Influenza Virus to the Respiratory Epithelium of Pigs Enhance Sialic Acid Binding Activity and Virulence in Mice

Initial steps of the pathogenesis of the infection caused byStreptococcus suis: fighting against nonspecific defenses

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