Polio, HIV, Genomes and Prions
 Save money – eradicate polioGetting close to eradication polio has cost more than $5 billion, and the WHO predicts that completely eradicating the virus will cost another $1.5 billion. Vaccinating enough people to keep the virus to its current low levels over the next 20 years would cost more than eradication. A low-cost control policy that relies only on routine immunisation for 20 years with costs of more than $3500 million could lead to roughly 200,000 paralytic poliomyelitis cases every year in low-income countries, whereas a low-case control policy that keeps the number of cases at about 1500 per year could cost around $10,000 million discounted over the 20 years. Eradication versus control for poliomyelitis: an economic analysis. |
 HIV Rev protein enhances encapsidationThe AIDS pandemic is still an important public health problem, particularly in developing countries. A comprehensive understanding of the HIV replication cycle might allow development of new therapeutics. Despite 20 years of extensive research, the intracellular fate of the different RNAs produced during virus replication is not fully understood. It is known that the viral regulatory protein Rev binds to large viral RNAs and shuttles them from the nucleus to the cytoplasm by a cellular export pathway. We now provide evidence for a more far-reaching role of Rev. We observed that Rev enhances packaging of viral RNA into viral particles to a much larger extent than its effect on viral RNA levels in the cytoplasm. Thus, an early nuclear event (binding of Rev to the viral RNA) seems to be intimately linked to RNA encapsidation occurring at a late step of the viral replication cycle. Since Rev is not part of the viral particles, Rev seems to act indirectly, possibly by targeting the viral RNA to a cytoplasmic compartment favourable for RNA encapsidation. Thus, further studies on the function of Rev might also advance our understanding of cytoplasmic RNA trafficking and subcytoplasmic compartmentalization. |
 Syntrophus aciditrophicus: Life at the thermodynamic limit of microbial growthThe bacterium Syntrophus aciditrophicus lives on a diet so austere that it exists on the brink of energetic death. The entire genome sequence of this bacterium provides clues as to how it survives, and might even improve the efficiency by which we can make hydrogen from waste materials: Biochemically, the syntrophic bacteria constitute the missing link in our understanding of anaerobic flow of carbon in the biosphere. The completed genome sequence of Syntrophus aciditrophicus provides a glimpse of the composition and architecture of the electron transfer and energy-transducing systems needed to exist on marginal energy economies of a syntrophic lifestyle. The genome contains 3,179,300 base pairs and 3,169 genes where 1,618 genes were assigned putative functions. Metabolic reconstruction of the gene inventory revealed that most biosynthetic pathways of a typical Gram-negative microbe were present. A distinctive feature of syntrophic metabolism is the need for reverse electron transport. Genomic analysis confirms the S. aciditrophicus metabolic and regulatory commitment to a nonconventional mode of life compared with our prevailing understanding of microbiology. The genome of Syntrophus aciditrophicus: Life at the thermodynamic limit of microbial growth. |
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 vCJD from dental treatment?Research suggests that between 1 in 1,400 and 1 in 20,000 people in the UK may be carrying variant CJD without showing any symptoms. Now UK dentists have been told not to re-use instruments for root canal work because of a possibility they could infect patients with vCJD. The government’s chief dental officer for England said there had been no cases of transmission, but research had shown a potential risk. The ban applies to instruments known as files and reamers used in endodontic procedures, most often to remove dead or damaged tissue from the root canal of a tooth. There are approximately one million NHS endodontic treatments every year in England and Wales (do the maths). Dr Barry Cockcroft, the chief dental officer for England, said: “There are no reported definite or suspected cases of vCJD transmission arising from dental procedures. This new guidance to dentists is purely an extra precaution. The public should continue to attend their dentist as normal.” |
 Use of thermolysin in the diagnosis of prion diseasesThe molecular diagnosis of prion diseases almost always involves the use of a protease to distinguish PrPC from PrPSc and invariably the protease of choice is proteinase K. Here, we have applied the protease thermolysin to the diagnosis of animal prion diseases. This thermostable protease cleaves at the hydrophobic residues Leu, Ile, Phe, Val, Ala, and Met, residues that are absent from the protease accessible aminoterminal region of PrPSc. Therefore, although thermolysin readily digests PrPC into small protein fragments, full-length PrPSc is resistant to such proteolysis. This contrasts with proteinase K digestion where an aminoterminally truncated PrPSc species is produced, PrP27-30. Thermolysin was used in the diagnosis of ovine scrapie and bovine spongiform encephalopathy and produced comparable assay sensitivity to assays using proteinase K digestion. Furthermore, we demonstrated the concentration of thermolysin-resistant PrPSc using immobilized metal-affinity chromatography. The use of thermolysin to reveal a full-length PrPSc has application for the development of novel immunodiagnostics by exploiting the wide range of commercially available immunoreagents and metal affinity matrices that bind the amino-terminal region of PrP. In addition, thermolysin provides a complementary tool to proteinase K to allow the study of the contribution of the amino-terminal domain of PrPSc to disease pathogenesis. |
 A 25 nm virion may be the cause of transmissible spongiform encephalopathies?The transmissible spongiform encephalopathies (TSEs) such as endemic sheep scrapie, sporadic human Creutzfeldt-Jakob disease (CJD), and epidemic bovine spongiform encephalopathy (BSE) may all be caused by a unique class of “slow” viruses. This concept remains the most parsimonious explanation of the evidence to date, and correctly predicted the spread of the BSE agent to vastly divergent species. With the popularization of the prion (infectious protein) hypothesis, substantial data pointing to a TSE virus have been largely ignored. Yet no form of prion protein (PrP) fulfills Koch’s postulates for infection. Pathologic PrP is not proportional to, or necessary for infection, and recombinant and “amplified” prions have failed to produce significant infectivity. Moreover, the “wealth of data” claimed to support the existence of infectious PrP are increasingly contradicted by experimental observations, and cumbersome speculative notions, such as spontaneous PrP mutations and invisible strain-specific forms of “infectious PrP” are proposed to explain the incompatible data. The ability of many “slow” viruses to survive harsh environmental conditions and enzymatic assaults, their stealth invasion through protective host-immune defenses, and their ability to hide in the host and persist for many years, all fit nicely with the characteristics of TSE agents. Highly infectious preparations with negligible PrP contain nucleic acids of 1-5 kb, even after exhaustive nuclease digestion. Sedimentation as well as electron microscopic data also reveal spherical infectious particles of 25-35 nm in diameter. This particle size can accommodate a viral genome of 1-4 kb, sufficient to encode a protective nucleocapsid and/or an enzyme required for its replication. Host PrP acts as a cellular facilitator for infectious particles, and ultimately accrues pathological amyloid features. A most significant advance has been the development of tissue culture models that support the replication of many different strains of agent and can produce high levels of infectivity. These models provide new ways to rapidly identify intrinsic viral and strain-specific molecules so important for diagnosis, prevention, and fundamental understanding. J Cell Biochem 2007 100: 897-915 Hmmm – I’ll believe this when these mysterious “virions” are shown to fulfill Koch’s Postulates. |
Thank you for the research report about HIV. I’ve been living with HIV for 5 years. Any research result is hope.
My personal HIV blog: http://www.positivesingles.com/blog/monemagic