Y leptospiral cells. This investment and the high level of LipL32 amino acid sequence conservation [41] suggests an important functional role in pathogenic Leptospira cells. Although immunization by LipL32 did not elicit protection in hamsters [35] and LipL32 is not required for either acute or chronic infection by L. interrogans [36], it should not be assumed that this protein is unimportant for leptospires in vivo. In fact, LipL32 is expressed at high levels during infection based on antibody reactivity with LipL32 in 94 of convalescent sera from leptospirosis patients [42] and detection by immunohistochemistry in the kidney [17] and blood [43] of infected animals. Some studies [44,45] have reported that LipL32 can elicit strong immune response or even act as partially protective antigen when presented to immune system by certain delivery systems, such as Cholera toxin B subunit [44] or 1326631 Mycobacterium bovis BCG [45]. However, generation of antiLipL32 antibodies is not evidence for surface exposure as it is widely recognized that an immune response to immunogenic cytoplasmic proteins, such as GroEL and DnaK, frequently occurs during infection, including during leptospirosis [46]. It is possible that LipL32 function may be affected by posttranslational modification events. The carboxy-terminus of LipL32 undergoesproteolytic cleavage both in vitro [16] and in vivo [47]. Moreover, LipL32 is both phosphorylated and methylated [48], which warrants further studies on this intriguing protein. Despite the availability of detailed crystal structure data [49,50], the primary function(s) of LipL32 remain largely unknown. Nevertheless, we hope that our reassessment of this protein’s subcellular location will assist investigators in formulating and testing novel hypotheses regarding the role of LipL32 in pathogenic Leptospira species.AcknowledgmentsWe thank Drs. Jane T. Babbitt and James Matsunaga for useful discussions and Dr. Henry A. Choy for valuable assistance. We also thank Dr. Tubastatin-A chemical information Albert I. 
Ko for generous gift of leptospirosis patient serum samples, and Dr. Jose ?Antonio Guimaraes Aleixo for providing LipL32 monoclonal antibody 1D9.Author ContributionsConceived and designed the experiments: MP DAH. Performed the experiments: MP. Analyzed the data: MP DAH. Contributed reagents/ materials/analysis tools: DAH. Wrote the paper: MP.
Infectious disease diagnostics traditionally rely heavily on pathogen detection [1,2,3]. However, the development of reproducible means for extracting RNA from whole blood, coupled with advanced statistical methods for analysis of complex datasets, has created the possibility of classifying infections based on host gene expression profiling. We recently developed a robust whole blood mRNA expression classifier for human respiratory viral infection at the time of maximal symptoms using data from three human viral challenge cohorts (rhinovirus, respiratory syncytial virus, and H3N2 influenza A) [4]. Sparse latent factor analysis of peripheral blood mRNA expression data revealed a buy Anlotinib pattern of geneexpression common across symptomatic individuals from all viral challenges [4]. Furthermore, an analysis of publically available peripheral blood-based gene expression data indicated that the respiratory viral signature could distinguish patients with symptomatic viral infections from those with bacterial infections as well as from healthy controls [4,5]. The emergence of pandemic H1N1 influenza in 2009 highlights the need for new.Y leptospiral cells. This investment and the high level of LipL32 amino acid sequence conservation [41] suggests an important functional role in pathogenic Leptospira cells. Although immunization by LipL32 did not elicit protection in hamsters [35] and LipL32 is not required for either acute or chronic infection by L. interrogans [36], it should not be assumed that this protein is unimportant for leptospires in vivo. In fact, LipL32 is expressed at high levels during infection based on antibody reactivity with LipL32 in 94 of convalescent sera from leptospirosis patients [42] and detection by immunohistochemistry in the kidney [17] and blood [43] of infected animals. Some studies [44,45] have reported that LipL32 can elicit strong immune response or even act as partially protective antigen when presented to immune system by certain delivery systems, such as Cholera toxin B subunit [44] or 1326631 Mycobacterium bovis BCG [45]. However, generation of 
antiLipL32 antibodies is not evidence for surface exposure as it is widely recognized that an immune response to immunogenic cytoplasmic proteins, such as GroEL and DnaK, frequently occurs during infection, including during leptospirosis [46]. It is possible that LipL32 function may be affected by posttranslational modification events. The carboxy-terminus of LipL32 undergoesproteolytic cleavage both in vitro [16] and in vivo [47]. Moreover, LipL32 is both phosphorylated and methylated [48], which warrants further studies on this intriguing protein. Despite the availability of detailed crystal structure data [49,50], the primary function(s) of LipL32 remain largely unknown. Nevertheless, we hope that our reassessment of this protein’s subcellular location will assist investigators in formulating and testing novel hypotheses regarding the role of LipL32 in pathogenic Leptospira species.AcknowledgmentsWe thank Drs. Jane T. Babbitt and James Matsunaga for useful discussions and Dr. Henry A. Choy for valuable assistance. We also thank Dr. Albert I. Ko for generous gift of leptospirosis patient serum samples, and Dr. Jose ?Antonio Guimaraes Aleixo for providing LipL32 monoclonal antibody 1D9.Author ContributionsConceived and designed the experiments: MP DAH. Performed the experiments: MP. Analyzed the data: MP DAH. Contributed reagents/ materials/analysis tools: DAH. Wrote the paper: MP.
Infectious disease diagnostics traditionally rely heavily on pathogen detection [1,2,3]. However, the development of reproducible means for extracting RNA from whole blood, coupled with advanced statistical methods for analysis of complex datasets, has created the possibility of classifying infections based on host gene expression profiling. We recently developed a robust whole blood mRNA expression classifier for human respiratory viral infection at the time of maximal symptoms using data from three human viral challenge cohorts (rhinovirus, respiratory syncytial virus, and H3N2 influenza A) [4]. Sparse latent factor analysis of peripheral blood mRNA expression data revealed a pattern of geneexpression common across symptomatic individuals from all viral challenges [4]. Furthermore, an analysis of publically available peripheral blood-based gene expression data indicated that the respiratory viral signature could distinguish patients with symptomatic viral infections from those with bacterial infections as well as from healthy controls [4,5]. The emergence of pandemic H1N1 influenza in 2009 highlights the need for new.
