Nutrition as a Critical Determinant in Susceptibility to Infection

2015 ◽  
pp. 166-188 ◽  
Author(s):  
R. K. Chandra
1998 ◽  
Vol 72 (8) ◽  
pp. 6475-6481 ◽  
Author(s):  
Brian J. Willett ◽  
Karen Adema ◽  
Nikolaus Heveker ◽  
Anne Brelot ◽  
Laurent Picard ◽  
...  

ABSTRACT The feline homolog of the α-chemokine receptor CXCR4 has recently been shown to support cell-cell fusion mediated by CXCR4-dependent strains of human immunodeficiency virus (HIV) and strains of feline immunodeficiency virus (FIV) that have been selected for growth in the Crandell feline kidney (CrFK) cell line. In this report we demonstrate that expression of CXCR4 alone is sufficient to render cells from diverse species permissive for fusion with FIV-infected cells, suggesting that CXCR4 is the sole receptor for CrFK-tropic strains of FIV, analogous to CD4-independent strains of HIV-2. To identify the regions of CXCR4 involved in fusion mediated by FIV, we screened panels of chimeric CXCR4 molecules for the ability to support fusion with FIV-infected cells. Human CXCR4 supported fusion more efficiently than feline CXCR4 and feline/human CXCR4 chimeras, suggesting that the second and third extracellular loops of human CXCR4 contain a critical determinant for receptor function. Rat/human CXCR4 chimeras suggested that the second extracellular loop contained the principal determinant for receptor function; however, chimeras constructed between human CXCR2 and CXCR4 revealed that the first and third loops of CXCR4 contribute to the FIV Env binding site, as replacement of these domains with the corresponding domains of CXCR2 rendered the molecule nonfunctional in fusion assays. Mutation of the DRY motif and the C-terminal cytoplasmic tail of CXCR4 did not affect the ability of the molecule to support fusion, suggesting that neither signalling via G proteins nor receptor internalization was required for fusion mediated by FIV; similarly, truncation of the N terminus of CXCR4 did not affect the function of the molecule as a receptor for FIV. CXCR4-transfected feline cells were rendered permissive for infection with both the CrFK-tropic PET isolate of FIV and the CXCR4-dependent RF strain of HIV-1, and susceptibility to infection correlated well with ability to support fusion. The data suggest that the second extracellular loop of CXCR4 is the major determinant of CXCR4 usage by FIV.


2020 ◽  
Vol 5 ◽  

Human leukocyte antigen (HLA) loci are highly polymorphic and determine differential features of the immune response in subjects from different regions. HLA genes have been proposed to determine genetic susceptibility to several diseases, particularly to viral infections. Moreover, it has been suggested that each ethnic group could have a different specificity of T-lymphocyte reactivity to the same viral infections. In this review, we analyzed the distribution of HLA types in countries of the Asian, European and North African region. Also, we studied the relation between these HLA polymorphisms and susceptibility to infection by the coronavirus. Our findings indicated that homozygosity would increase susceptibility to viral infections and, in some cases, to coronavirus infection. HLA types showing higher susceptibility were reported in Asian population, including China, Singapore, and Taiwan. In contrast, lower susceptibility HLA variants were detected among African populations, some Asian populations, and Mediterranean populations. The presented evidence along with the spread pattern of COVID-19 infection suggests that HLA genetic variants might be related to its infection susceptibility and severity. The investigation of HLA genetic variants distribution would be a useful tool to predict different populations’ susceptibility to viral infections.


2007 ◽  
Vol 30 (4) ◽  
pp. 93
Author(s):  
I Sekirov ◽  
N Tam ◽  
M Robertson ◽  
C Lupp ◽  
B Finlay

Background: During our lifetimes we develop a very complex set of interactions with the multitude of microorganisms colonizing our bodies. In the gastrointestinal system, the microbiota is highly important for morphological development, nutrition, and protection against infectious diseases. The gastrointestinal pathogens, enterohemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC) and Salmonella enterica serovar Typhimurium (ST) are food-borne pathogens that cause much morbidity and mortality worldwide. Citrobacter rodentium (Cr) is a mouse pathogen that is used in small animal models to mimic EHEC and EPEC infections. Methods: We began to characterize the contribution of intestinal microbiota to the progression of these infections. Two main phyla comprise the majority of mouse intestinal microbiota: Bacteroidetes and Firmicutes. Bacteria from a number of additional phyla are also present in smaller numbers; among them γ-Proteobacteria class, belonging to Proteobacteria phylum, is note-worthy as this class harbours many intestinal pathogens, such as ST and Cr. The mouse intestinal microbiota was perturbed using tetracycline (Tet) and streptomycin (Sm) to increase the proportion of Bacteroidetes in the colonic microbiota, and using vancomycin (Vanc) to create a predominance of Firmicutes. The mice with this perturbed microbiota were infected with ST to investigate the resultant pathology and virulence characteristics, and any additional shifts in microbiota as a result of infection. Results: Treatment of mice with Sm and Vanc was found to decrease the resistance of mice to colonization with ST, while Tet-treated mice exhibited unchanged colonization resistance. Treatment of mice with gradually increasing doses of Sm, which gradually augmented the proportion of CFB bacteria in the microbiota, resulted in progressively increasing colonization of mice by ST, as well as a step-wise increase in the ST-induced typhlitis, associated with higher levels of inflammatory markers IL-6 and KC. The increasing levels of ST colonization following both Sm and Vanc treatment were associated with an increase in the proportion of γ-Proteobacteria in the cecal and colonic microbiota, as well as a decrease in the total bacterial numbers in both organs. Conclusions: It is evident that the intestinal microbiota plays a significant role in the host’s response to infection with enteric pathogens, and its composition and numbers are also affected by the offending bacteria. Elucidation of the details regarding the contribution of the microbiota to infectious disease progression will offer novel targets for the future design of superior prevention and treatment methods.


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