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. 2022 Jan 21;17(1):e0261689.
doi: 10.1371/journal.pone.0261689. eCollection 2022.

Effects of antibiotic treatment on microbiota, viral transmission and viral pathogenesis of MoMuLV ts1 infected BALB/c mice

Henry Okonta  1 , Xi Cheng  2 , Ritu Chakravarti  2 , Joan Duggan  1
Affiliations

Effects of antibiotic treatment on microbiota, viral transmission and viral pathogenesis of MoMuLV ts1 infected BALB/c mice

Henry Okonta et al. PLoS One. .

Abstract

The effects of normal and altered intestinal microbiota on murine retroviral transmission via the gastrointestinal tract (GIT) are diverse. The role of orally administered antibiotic treatment (ABX) on viral transmission, GIT microbial dysbiosis and subsequent pathogenesis of Moloney Murine Leukemia virus-temperature sensitive 1 (ts1) on BALB/c mice were studied. BALB/c mice were divided into four groups: ABXts1-Treatment/Infection;ABX-Treatment/No infection;ts1-No treatment/Infection;Ctrl (control)-No treatment/No infection. ABXts1 and ABX groups showed a significant phylogenetic shift (ANOSIM p-value = 0.001) in alpha and beta diversity comparisons for microbial community composition compared to Ctrl group. Mice in the ABXts1 and ABX groups showed megacolon compared to ts1 and Ctrl groups; ABXts1 and ts1 groups showed hepatosplenomegaly, thymus enlargement, and mesenteric lymphadenopathy compared to ABX and Ctrl groups. Ctrl group had no abnormal manifestations. ABX treatment and ts1 infection uniquely affect microbial community when compared to control: ABXts1 and ABX groups significantly reduce microbiome diversity by over 80% and ts1 group by over 30%. ABXts1 and ts1 groups' viral load and clinical manifestations of infection were comparable; antibiotic treatment did not notably affect ts1 infection. Transmission and pathophysiology of ts1 infection were not significantly altered by the microbial composition of the GI tract, but ts1 viral infection did result in microbial dysbiosis independent of antibiotic treatment.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Summary of cecal microbiome diversity and taxa differential abundance analyses.
(Fig 1A) Average α-diversity. All values are expressed as mean ± standard deviation. (Fig 1B) Unweighted β-diversity (ANOSIM p-value = 0.001). (Fig 1C) Weighted β-diversity (ANOSIM p-value = 0.001); (Fig 1D) Relative abundance of bacterial phyla. (Fig 1E) Cladogram showing enriched bacterial taxa with their phylogenetic relationships. (Fig 1F) LEfSe plot showing enriched bacterial taxa in each group. Bacterial taxa that have a linear discriminant analysis (LDA) score greater than 2.0 are considered to be significantly differential.
Fig 2
Fig 2. Antibiotic independent viral growth.
Average peripheral blood ts1 titer for all groups (Fig 2A) were measured and compared to uninfected control. Average body weights (Fig 2B), spleen weights (Fig 2C) thymus weights (Fig 2D), mesenteric lymph node weights (Fig 2E) and cecum weights (Fig 2F) in ABXts1, ABX, and ts1 groups were measured and compared to control (Ctrl).
Fig 3
Fig 3. Anatomic and histologic changes due to viral infection and antibiotic treatment.
Anatomic changes showing spleen, thymus and cecum from Control (Fig 3A), ts1 infected (Fig 3B), ABX treated (Fig 3C) and ABXts1 treated and infected (Fig 3D) animals. Spleen architecture with normal distribution of discrete red pulp (RP) and white pulp (WP) regions for control (Fig 3E) and ABX treated (Fig 3G). Mice infected with ts1 (Fig 3F) and ABXts1 treated and infected animals (Fig 3H), show disorganized red and white pulp regions. Thymic capsule, cortex and medulla among the various groups: control (Fig 3J) and ABX treated (Fig 3L) show intact capsule and distinct areas of the cortex (deep purple) and medulla (lighter purple) of thymus; ts1 infected (Fig 3K) and ABXts1 treated and infected animals (Fig 3M) were fragile, with ill-defined capsule and diffused cortex and medulla regions. Colon (Fig 3N, 3P, 3Q and 3R): Normal muscularis tunics (MT), muscularis externa (ME), muscularis mucosae (MM), crypts (C) of colon in control (Fig 3N) and ts1 infected (Fig 3P) animals. Expanded or broad layers of muscularis tunics (MT), muscularis externa (ME) and muscularis mucosae (MM) with narrowed crypts (C) of colon in ABX treated (Fig 3Q) and ABXts1 treated and infected (Fig 3R) animals.
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