Related enteric viruses have different requirements for host microbiota in mice

AbstractAccumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, like poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. Quantity and composition of bacterial communities were altered by treatment with the five antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis, while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 is more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ in their reliance on microbiota.ImportanceRecent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that microbiota can influence enteric virus infection through distinct mechanisms, even for closely related viruses.

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Related Enteric Viruses Have Different Requirements for Host Microbiota in Mice

Journal of Virology ◽

10.1128/jvi.01339-19 ◽

2019 ◽

Vol 93 (23) ◽

Cited By ~ 8

Author(s):

Christopher M. Robinson ◽

Mikal A. Woods Acevedo ◽

Broc T. McCune ◽

Julie K. Pfeiffer

Keyword(s):

Single Dose ◽

Viral Replication ◽

Antibiotic Treatment ◽

Enteric Viruses ◽

Intestinal Bacteria ◽

Enteric Virus ◽

Intestinal Infection ◽

Bacterial Populations ◽

Antibiotic Cocktail ◽

Oral Inoculation

ABSTRACT Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here, we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, as seen with poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. The quantity and composition of bacterial communities were altered by treatment with the five-antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more-subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the standard concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 are more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ with respect to their reliance on microbiota. IMPORTANCE Recent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here, we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that closely related viruses may differ with respect to their reliance on microbiota.

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Bacteria facilitate viral co-infection of mammalian cells and promote genetic recombination

10.1101/154021 ◽

2017 ◽

Cited By ~ 2

Author(s):

A.K. Erickson ◽

P.R. Jesudhasan ◽

M.J. Mayer ◽

A. Narbad ◽

S.E. Winter ◽

...

Keyword(s):

Mammalian Cells ◽

Genetic Recombination ◽

Enteric Viruses ◽

Intestinal Bacteria ◽

Enteric Virus ◽

Viral Fitness ◽

Host Cells ◽

Bacterial Strains ◽

Viral Recombination ◽

Viral Genomes

SUMMARYIntestinal bacteria promote infection of several mammalian enteric viruses, but the mechanisms and consequences are unclear. We screened a panel of 41 bacterial strains as a platform to determine how different bacteria impact enteric viruses. We found that most bacterial strains bound poliovirus, a model enteric virus. Given that each bacterium bound multiple virions, we hypothesized that bacteria may deliver multiple viral genomes to a mammalian cell even when very few virions are present, such as during the first replication cycle after inter-host transmission. We found that exposure to certain bacterial strains increased viral co-infection even when the ratio of virus to host cells was low. Bacteria-mediated viral co-infection correlated with bacterial adherence to cells. Importantly, bacterial strains that induced viral co-infection facilitated viral fitness restoration through genetic recombination. Thus, bacteria-virus interactions may increase viral fitness through viral recombination at initial sites of infection, potentially limiting abortive infections.

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Microbiota-Independent Antiviral Effects of Antibiotics on Enteric Viruses

10.1101/2020.02.14.949123 ◽

2020 ◽

Author(s):

Mikal A. Woods Acevedo ◽

Julie K. Pfeiffer

Keyword(s):

Antibiotic Treatment ◽

Severe Disease ◽

Enteric Viruses ◽

Systemic Infection ◽

Enteric Virus ◽

Intestinal Microbes ◽

Treatment Regimens ◽

Antiviral Effects ◽

Cvb3 Infection ◽

Independent Mechanism

AbstractCoxsackieviruses primarily infect the gastrointestinal tract of humans, but they can disseminate systemically and cause severe disease. Using antibiotic treatment regimens to deplete intestinal microbes in mice, several groups have shown that bacteria promote oral infection with a variety of enteric viruses. However, it is unknown whether antibiotics have microbiota-independent antiviral effects for enteric viruses or whether antibiotics influence extra-intestinal, systemic infection. Here, we examined the effects of antibiotics on systemic enteric virus infection by performing intraperitoneal injections of either coxsackievirus B3 (CVB3) or poliovirus followed by quantification of viral titers. We found that antibiotic treatment reduced systemic infection for both viruses. Interestingly, antibiotics reduced CVB3 titers in germ-free mice, suggesting that antibiotic treatment alters CVB3 infection through a microbiota-independent mechanism. Overall, these data provide further evidence that antibiotics can have noncanonical effects on viral infection.

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Enteric viruses in drinking water supplies

Water Science & Technology Water Supply ◽

10.2166/ws.2002.0080 ◽

2002 ◽

Vol 2 (3) ◽

pp. 17-22

Author(s):

A.P. Wyn-Jones ◽

J. Watkins ◽

C. Francis ◽

M. Laverick ◽

J. Sellwood

Keyword(s):

Drinking Water ◽

Heavy Rainfall ◽

Liquid Culture ◽

Plaque Assay ◽

Enteric Viruses ◽

Enteric Virus ◽

The Other ◽

Raw Water ◽

Rt Pcr ◽

Water Supplies

Two rural spring drinking water supplies were studied for their enteric virus levels. In one, serving about 30 dwellings, the water was chlorinated before distribution; in the other, which served a dairy and six dwellings the water was not treated. Samples of treated (40 l) and untreated (20 l) water were taken under normal and heavy rainfall conditions over a six weeks period and concentrated by adsorption/elution and organic flocculation. Infectious enterovirus in concentrates was detected in liquid culture and enumerated by plaque assay, both in BGM cells, and concentrates were also analysed by RT-PCR. Viruses were found in both raw water supplies. Rural supplies need to be analysed for viruses as well as bacterial and protozoan pathogens if the full microbial hazard is to be determined.

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Measurement of the Intestinal pH in Mice under Various Conditions Reveals Alkalization Induced by Antibiotics

Antibiotics ◽

10.3390/antibiotics10020180 ◽

2021 ◽

Vol 10 (2) ◽

pp. 180

Author(s):

Kouki Shimizu ◽

Issei Seiki ◽

Yoshiyuki Goto ◽

Takeshi Murata

Keyword(s):

Antibiotic Treatment ◽

High Protein Diet ◽

Intestinal Bacteria ◽

High Protein ◽

Protein Diet ◽

Germ Free ◽

Treatment Regimens ◽

Ph Values ◽

Specific Pathogen ◽

The Stability

The intestinal pH can greatly influence the stability and absorption of oral drugs. Therefore, knowledge of intestinal pH is necessary to understand the conditions for drug delivery. This has previously been measured in humans and rats. However, information on intestinal pH in mice is insufficient despite these animals being used often in preclinical testing. In this study, 72 female ICR mice housed in SPF (specific pathogen-free) conditions were separated into nine groups to determine the intestinal pH under conditions that might cause pH fluctuations, including high-protein diet, ageing, proton pump inhibitor (PPI) treatment, several antibiotic treatment regimens and germ-free mice. pH was measured in samples collected from the ileum, cecum and colon, and compared to control animals. An electrode, 3 mm in diameter, enabled accurate pH measurements with a small amount of gastrointestinal content. Consequently, the pH values in the cecum and colon were increased by high-protein diet, and the pH in the ileum was decreased by PPI. Drastic alkalization was induced by antibiotics, especially in the cecum and colon. The alkalized pH values in germ-free mice suggested that the reduction in the intestinal bacteria caused by antibiotics led to alkalization. Alkalization of the intestinal pH caused by antibiotic treatment was verified in mice. We need further investigations in clinical settings to check whether the same phenomena occur in patients.

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Antibiotic treatment with one single dose of gentamicin at admittance in addition to a β-lactam antibiotic in the treatment of community-acquired bloodstream infection with sepsis

PLoS ONE ◽

10.1371/journal.pone.0236864 ◽

2020 ◽

Vol 15 (7) ◽

pp. e0236864 ◽

Cited By ~ 1

Author(s):

Karolina Liljedahl Prytz ◽

Mårten Prag ◽

Hans Fredlund ◽

Anders Magnuson ◽

Martin Sundqvist ◽

...

Keyword(s):

Single Dose ◽

Bloodstream Infection ◽

Antibiotic Treatment ◽

Lactam Antibiotic

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Assessing the Occurrence of Waterborne Viruses in Reuse Systems: Analytical Limits and Needs

Pathogens ◽

10.3390/pathogens8030107 ◽

2019 ◽

Vol 8 (3) ◽

pp. 107 ◽

Cited By ~ 2

Author(s):

Charles P. Gerba ◽

Walter Q. Betancourt

Keyword(s):

Cell Culture ◽

Virus Detection ◽

Enteric Viruses ◽

Enteric Virus ◽

Culture Cell ◽

Virus Infectivity ◽

Recycled Water ◽

Chemical Additives ◽

Potable Reuse ◽

Passage Number

Detection of waterborne enteric viruses is an essential tool in assessing the risk of waterborne transmission. Cell culture is considered a gold standard for detection of these viruses. However, it is important to recognize the uncertainty and limitations of enteric virus detection in cell culture. Cell culture cannot support replication of all virus types and strains, and numerous factors control the efficacy of specific virus detection assays, including chemical additives, cell culture passage number, and sequential passage of a sample in cell culture. These factors can result in a 2- to 100-fold underestimation of virus infectivity. Molecular methods reduce the time for detection of viruses and are useful for detection of those that do not produce cytopathogenic effects. The usefulness of polymerase chain reaction (PCR) to access virus infectivity has been demonstrated for only a limited number of enteric viruses and is limited by an understanding of the mechanism of virus inactivation. All of these issues are important to consider when assessing waterborne infectious viruses and expected goals on virus reductions needed for recycled water. The use of safety factors to account for this may be useful to ensure that the risks in drinking water and recycled water for potable reuse are minimized.

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Enteric Viruses and Inflammatory Bowel Disease

Viruses ◽

10.3390/v13010104 ◽

2021 ◽

Vol 13 (1) ◽

pp. 104

Author(s):

Georges Tarris ◽

Alexis de Rougemont ◽

Maëva Charkaoui ◽

Christophe Michiels ◽

Laurent Martin ◽

...

Keyword(s):

Association Studies ◽

Enteric Viruses ◽

Enteric Virus ◽

Viral Gastroenteritis ◽

Blood Group Antigens ◽

Genome Wide Association Studies ◽

Virus Infections ◽

T Helper ◽

Inflammatory Bowel

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a multifactorial disease in which dietary, genetic, immunological, and microbial factors are at play. The role of enteric viruses in IBD remains only partially explored. To date, epidemiological studies have not fully described the role of enteric viruses in inflammatory flare-ups, especially that of human noroviruses and rotaviruses, which are the main causative agents of viral gastroenteritis. Genome-wide association studies have demonstrated the association between IBD, polymorphisms of the FUT2 and FUT3 genes (which drive the synthesis of histo-blood group antigens), and ligands for norovirus and rotavirus in the intestine. The role of autophagy in defensin-deficient Paneth cells and the perturbations of cytokine secretion in T-helper 1 and T-helper 17 inflammatory pathways following enteric virus infections have been demonstrated as well. Enteric virus interactions with commensal bacteria could play a significant role in the modulation of enteric virus infections in IBD. Based on the currently incomplete knowledge of the complex phenomena underlying IBD pathogenesis, future studies using multi-sampling and data integration combined with new techniques such as human intestinal enteroids could help to decipher the role of enteric viruses in IBD.

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