مقالات

Microbial Genomics and Infectious Diseases

نویسنده :
تاریخ انتشار : 1397/04/13
The pace of technical advancement in microbial genomics has been breathtaking. Since 1995, when the first complete genome sequence of a free-living organism, Haemophilus influenzae, was published,1 1554 complete bacterial genome sequences (the majority of which are from pathogens) and 112 complete archaeal genome sequences have been determined, and more than 4800 and 90, respectively, are in progress.2 A total of 41 complete eukaryotic genome sequences have been determined (19 from fungi), and more than 1100 are in progress. Complete reference genome sequences are available for 2675 viral species, and for some of these species, a large number of strains have been completely sequenced. Nearly 40,000 strains of influenza virus3 and more than 300,000 strains of human immunodeficiency virus (HIV) type 1 have been partially sequenced.4 However, the selection of microbes and viruses for genome sequencing is heavily biased toward the tiny minority that are amenable to cultivation in the laboratory, numerically dominant in particular habitats of interest (e.g., the human body), and associated with disease. In 2006, investigators reported in-depth metagenomic sequence data from a human mixed microbial community5; in 2007 more than 1000 genes from single cells of cultivation-resistant bacteria were identified.6 Since then, a flood of such data has ensued (Fig. 1).7-9 Individual investigators can now produce a draft sequence of a bacterial genome containing 4 million base pairs in about a day.10-12 The revolution in DNA-sequencing technology has to a large extent democratized microbial genomics and altered the way infectious diseases are studied.11 However, gene annotation and error correction still take time and effort. Today, the major challenges in microbial genomics are to predict the function of gene products and the behavior of organisms and communities from their sequences and to use genomic data to develop improved tools for managing infectious diseases.

Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

نویسنده :
تاریخ انتشار : 1397/04/11
Zika virus (ZIKV) is an emerging flavivirus that can cause birth defects and neurologic complications. Molecular tests are effective for diagnosing acute ZIKV infection, although the majority of infections produce no symptoms at all or present after the narrow window in which molecular diagnostics are dependable. Serology is a reliable method for detecting infections after the viremic period; however, most serological assays have limited specificity due to cross-reactive antibodies elicited by flavivirus infections. Since ZIKV and dengue virus (DENV) widely cocirculate, distinguishing ZIKV infection from DENV infection is particularly important for diagnosing individual cases or for surveillance to coordinate public health responses. Flaviviruses also elicit type-specific antibodies directed to non-cross-reactive epitopes of the infecting virus; such epitopes are attractive targets for the design of antigens for development of serological tests with greater specificity. Guided by comparative epitope modeling of the ZIKV envelope protein, we designed two recombinant antigens displaying unique antigenic regions on domain I (Z-EDI) and domain III (Z-EDIII) of the ZIKV envelope protein. Both the Z-EDI and Z-EDIII antigens consistently detected ZIKV-specific IgG in ZIKV-immune sera but not cross-reactive IgG in DENVimmune sera in late convalescence (12 weeks postinfection). In contrast, during early convalescence (2 to 12 weeks postinfection), secondary DENV-immune sera and some primary DENV-immune sera cross-reacted with the Z-EDI and Z-EDIII antigens. Analysis of sequential samples from DENV-immune individuals demonstrated that Z-EDIII cross-reactivity peaked in early convalescence and declined steeply over time. The Z-EDIII antigen has much potential as a diagnostic antigen for populationlevel surveillance and for detecting past infections in patients.