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Journal Highlights

More Evidence for Role of Genetics in Immune Response to TB

Tuberculosis strikes an estimated 8 million people annually, and kills 2 to 3 million. Twin studies have consistently suggested that genetics influences immune response. Annette Jepson of the Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom, and others present new evidence for this from a study of 255 adult twin pairs in Africa. ". . . memory T-cell responses to secreted mycobacterial antigens (85-kDa antigen complex, "short-term culture filtrate" and peptides from the ESAT-6 protein) as well as to the 65-kDa heat shock protein, are subject to effective genetic regulation," the authors write. But ". . . quantitative T-cell and antibody responses to the 38-kDa cell membrane protein appear to be determined largely by environmental factors." The findings have implications for further understanding of the genetic mechanisms that underlie disease susceptibility, and for vaccine development.

(A. Jepson, A. Fowler, W. Banya, M. Singh, S. Bennett, H. Whittle, and A. V. S. Hill. 2001. Genetic regulation of acquired immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa. Infect. Immun. 69:3989-3994.) Abstract | Full Text

Microbial String of Pearls: a Hot Spot for Novel Archaea

Huber

New molecular methods have revealed a great diversity of Archaea in low-to-moderate-temperature ecosystems. In these biotopes, they often contribute significantly to microbial communities. Nonetheless, their basic physiological and biochemical properties and their role in the environment remain largely obscure. Robert Huber and colleagues of the Universität Regensburg in Germany discovered a string-of-pearls-like, macroscopically visible structure floating in cold (10° C) sulfurous marsh water. "In each pearl (diameter, 0.5-3 mm), a microcolony of novel Archaea is enclosed by filament-forming bacteria, which also connect the pearls to each other" says Huber. "This newly discovered structure represents a unique form of microbial life." Future studies will focus on isolating and cultivating this new group and will include gene transfer investigations, life cycle studies, and studies of interactions between members of different domains.

(C. Rudolph, G. Wanner, and R. Huber. 2001. Natural communities of novel Archaea and bacteria growing in cold sulfurous springs with a string-of-pearls-like morphology. Appl. Environ. Microbiol. 67:2336-2344.) Abstract | Full Text

Visualizing Viruses in Motion

Ward

To determine how newly formed poxvirus particles move within infected cells, Brian Ward and Bernard Moss of the NIAID, NIH, replaced the viral gene encoding the B5R outer envelop protein with one that encodes that protein fused to the jellyfish green fluorescence protein. "Remarkably, the fusion protein substituted perfectly, and allowed us to visualize by fluorescence microscopy the real-time intracellular movement of virus particles," says Moss. Collecting images at one-frame-per-second intervals, Ward noted a start-and-stop movement at speed similar to cellular vesicles associated with microtubules. Furthermore, the microtubule depolymerizing drug, nocodazole, interrupted virion movement reversibly. "We suspect that the intracellular enveloped virions are connected to microtubules by a cellular motor. We hope to determine the protein link in future studies."

(B. M. Ward and B. Moss. 2001. Visualization of intracellular movement of vaccinia virus virions containing a green fluorescent protein-B5R membrane protein chimera. J. Virol. 75:4802.) Abstract | Full Text

To Malaria-Proof Mosquitoes

Vinetz and Tsai

Claudianos, Dessens, and Khater

Blood-sucking arthropods such as mosquitoes encase blood meals in a sac impregnated with chitin, the material of insect exoskeletons. Two papers this month confirm that chitinase is the tool that Plasmodium, the malaria parasite, uses to escape from the blood meal and infect the mosquito. Joseph M. Vinetz of the University of Texas Medical Branch, Galveston, and coworkers show through deletion mutations that intact chitinase is essential for mosquito infection in human malaria, and that the last 13 amino acids of the protein appear critical to enabling the parasite to secrete this invasive enzyme, while Johannes Dessens and colleagues of the Imperial College of Science, Technology, and Medicine, London, United Kingdom, show that chitinase is important, but not essential to the spread of rodent malaria. Dessens et al. identify and characterize a chitinase gene from the rodent malaria parasite, P. berghei, showing that it differs from the avian and human versions. Disrupting the gene reduced infectivity by up to 90%. Vinetz is working on three approaches to blocking malaria transmission: vaccines and drugs against chitinase, and transgenic mosquitos that would secrete chitinase inhibitors into the gut. Dessens says that parasites are resistant to the candidate malaria transmission blocking drug allosamidin and that his data suggest that this "could result from simple structural changes to chitinase molecules, and, consequently, could occur rapidly in the field under allosamidin pressure." He plans further studies of the structure of chitinase "to shed more light on this matter."

(Y.-L. Tsai, R. E. Hayward, R. C. Langer, D. A. Fidock, and J. M. Vinetz. 2001. Disruption of Plasmodium falciparum chitinase markedly impairs parasite invasion of mosquito midgut. Infect. Immun. 69:4048-4054; and J. T. Dessens, J. Mendoza, C. Claudianos, J. M. Vinetz, E. Khater, S. Hassard, G. R. Ranawaka, and R. E. Sinden. 2001. Knockout of the rodent malaria parasite chitinase PbCHT1 reduces infectivity to mosquitos. Infect. Immun. 69:4041-4047.) Abstract | Full Text

Do Bacteria Inhabit Our Blood?

Nikkari

Cultivation-independent laboratory approaches have revealed surprising diversity in the environment. The presence of bacterial DNA in circulating blood would have important implications for immune system surveillance and evolution, and for a possible, previously uncharacterized role of bacteria in idiopathic systemic disease, and there is growing evidence that bacteria may circulate in the blood of healthy individuals. Now, using a real-time PCR method with primers and a probe targeting conserved regions of bacterial 16S rDNA, Simo Nikkari and David A. Relman of Stanford University, Stanford, Calif., and others have detected bacterial DNA in blood of healthy individuals. But the results need to be confirmed, says Nikkari, and they "highlight the need for caution in interpreting results when using highly sensitive molecular assays to study specimens with small amounts of microbial DNA."

(S. Nikkari, I. J. McLaughlin, W. Bi, D. E. Dodge, and D. A. Relman. 2001. Does blood of healthy subjects contain bacterial ribosomal DNA? J. Clin. Microbiol. 39:1956-1959.) Abstract | Full Text

Specialized Protein Tethers EBV Genome to Host Chromosome for Replication

Geoffrey M. Wahl and others of the Salk Institute, La Jolla, Calif., show that a specialized protein from the Epstein-Barr virus (EBV) is responsible for tethering its genome to the host cell chromosome, apparently to insure that the viral DNA is replicated faithfully and maintained in appropriate copy numbers during host cell division. The findings likely apply to other mammalian viruses, as well as extrachromosomal circles that sometimes carry cancer-related genes, says Wahl. They may have application in development of anticancer agents, and vectors for gene therapy (see Current Topics, p. 347).

(T. Kanda, M. Otter, and G. M. Wahl. 2001. Coupling of mitotic chromosome tethering and replication competence in Epstein-Barr virus-based plasmids. Mol. Cell. Biol. 21:3576-3588.) Abstract | Full Text