ПОЯВЛЕНИЕ ЭКЗОТИЧЕСКИХ ПЕРЕНОСЧИКОВ АРБОВИРУСНЫХ ЛИХОРАДОК – НОВАЯ НЕДОСТАТОЧНО ОЦЕНИВАЕМАЯ БИОЛОГИЧЕСКАЯ УГРОЗА ЮЖНЫМ РЕГИОНАМ РОССИИ

Delivery of originators of infectious and parasitic illnesses on new territories can pass by means of mosquitoes which in modern conditions extend quickly. Getting on new territories they take roots and provide transfer of this or that originator. Or they provide initial case rate, and then viruses start to circulate among mosquitoes – natural representatives of local fauna. As it was with virus Denge delivered to Greece with mosquitoes Aedes aegypti. This kind of a mosquito by 1950 has been destroyed at the Black Sea coast of Caucasus. In the beginning of 21 centuries this kind again began to be found out in earlier free territories. Occurrence after 50-years absence of an effective carrier in the south of Russia is serious biological threat to epidemic well-being of the country in case of delivery of originators arbovirus infections.Завоз возбудителей инфекционных и паразитарных болезней на новые территории может проходить с помощью комаров, которые в современных условиях распространяются быстро. Попадая на новые территории, они укореняются и обеспечивают передачу того или иного возбудителя, либо они обеспечивают начальную заболеваемость, а затем вирусы начинают циркулировать среди комаров – естественных представителей местной фауны. Так было с вирусом Денге, завезенным в Грецию с комарами Aedes aegypti. Этот вид комара к 1950 г. был уничтожен на черноморском побережье Кавказа. В начале XXI в. этот вид вновь стал обнаруживаться на ранее свободных территориях. Появление после 50-летнего отсутствия эффективного переносчика на юге России является серьезной биологической угрозой эпидемическому благополучию страны в случае завоза возбудителей арбовирусных инфекций

Гипотеза о внеафриканском происхождении вируса иммунодефицита человека 1-го типа (ВИЧ -1)

Longitudinal co-evolution of human beings and pathogens resulted in polymorphism of Homo sapiens. CCR5Δ32 HIV-resistance allele is the exception to the rules. Recent origin of HIV-1 in Africa contradicted with the appearance of CCR5Δ32 allele in Northern Europe in previous ages.The author proposed non-contradictory theory of primary appearance of ancient HIV-1 in the Northern Europe 5-7 thousand years ago. The primary epidemics of HIV-infection had been stopped by the appearance of CCR5Δ32 mutation among the affected population. Re-emergence of HIV-1 nowadays resulted by the penetration of hibernated HIV-1 into population of drug addicts and homosexual men.Длительная ко-эволюция человека и возбудителей инфекционных болезней привела к полиморфизму человека и появлению генетической резистентности к ряду патогенов. Единственным исключением является вирус иммунодефицита человека 1-го типа (ВИЧ-1). Аллель CCR5Δ32 обеспечивает 99,9% невосприимчивость к заражению ВИЧ-1. Согласно принятой гипотезе, ВИЧ-1 появился только в середине ХХ в. в Африке. Столь короткий период циркуляции патогена в человеческой популяции недостаточен для выработки генетического механизма невосприимчивости. Эпицентром распространения мутации, обеспечивающей генетическую защиту от ВИЧ-1, является север Европы. Частота встречаемости CCR5Δ32 убывает по направлению с севера на юго-восток. Эта мутация не встречается среди африканцев, что противоречит гипотезе об африканском происхождении ВИЧ-1. Автор обосновывает гипотезу о первичном происхождении ВИЧ-1 на севере Европы 5–7 тысяч лет назад. Настоящая эпидемическая ситуация является не первой волной распространения ВИЧ-инфекции. Распространение ВИЧ-инфекции во 2-й половине ХХ в. связано с попаданием резерватного варианта ВИЧ-1 в популяцию иммунокомпрометированных наркоманов и гомосексуалов

Cholera and the Death of the Ancient Indus Civilization

The paper presents a hypothesis that the most probable cause of death of the ancient world Indus (Harappa) civilization was the epidemic of Asiatic cholera. A brief description of the Indus civilization that existed for two millennia (3300–1300 BC) is given. It is shown that the previously described factors for the decline of the thriving Indus civilization (climate change, shallowing of the Indus river and reduction in floods, catastrophic floods, drought, economic crisis, etc.) do not provide a consistent and comprehensive explanation of the causes of its death. Meanwhile, the natural environment and peculiarities of agriculture of the Indus civilization (annual floods affecting not only fields, but also sewage systems) created ideal conditions for the spread of water-borne cholera. The evolution of the Asiatic cholera agent is discussed. The results of paleogenomics study of this pathogen and their significance for the reconstruction of evolutionary events are briefly reviewed. The stages of evolution of Vibrio cholerae of the classical biovar are described, and possible mechanisms for the preservation of the pathogen during inter-epidemic period are considered. It is demonstrated that aside from cholera, other catastrophic, destructive epidemics are recorded in the history of mankind

Function of the ribosomal E-site: a mutagenesis study

Ribosomes synthesize proteins according to the information encoded in mRNA. During this process, both the incoming amino acid and the nascent peptide are bound to tRNA molecules. Three binding sites for tRNA in the ribosome are known: the A-site for aminoacyl-tRNA, the P-site for peptidyl-tRNA and the E-site for the deacylated tRNA leaving the ribosome. Here, we present a study of Escherichia coli ribosomes with the E-site binding destabilized by mutation C2394G of the 23S rRNA. Expression of the mutant 23S rRNA in vivo caused increased frameshifting and stop codon readthrough. The progression of these ribosomes through the ribosomal elongation cycle in vitro reveals ejection of deacylated tRNA during the translocation step or shortly after. E-site compromised ribosomes can undergo translocation, although in some cases it is less efficient and results in a frameshift. The mutation affects formation of the P/E hybrid site and leads to a loss of stimulation of the multiple turnover GTPase activity of EF-G by deacylated tRNA bound to the ribosome

Multifaceted Mechanism of Amicoumacin A Inhibition of Bacterial Translation

Amicoumacin A (Ami) halts bacterial growth by inhibiting the ribosome during translation. The Ami binding site locates in the vicinity of the E-site codon of mRNA. However, Ami does not clash with mRNA, rather stabilizes it, which is relatively unusual and implies a unique way of translation inhibition. In this work, we performed a kinetic and thermodynamic investigation of Ami influence on the main steps of polypeptide synthesis. We show that Ami reduces the rate of the functional canonical 70S initiation complex (IC) formation by 30-fold. Additionally, our results indicate that Ami promotes the formation of erroneous 30S ICs; however, IF3 prevents them from progressing towards translation initiation. During early elongation steps, Ami does not compromise EF-Tu-dependent A-site binding or peptide bond formation. On the other hand, Ami reduces the rate of peptidyl-tRNA movement from the A to the P site and significantly decreases the amount of the ribosomes capable of polypeptide synthesis. Our data indicate that Ami progressively decreases the activity of translating ribosomes that may appear to be the main inhibitory mechanism of Ami. Indeed, the use of EF-G mutants that confer resistance to Ami (G542V, G581A, or ins544V) leads to a complete restoration of the ribosome functionality. It is possible that the changes in translocation induced by EF-G mutants compensate for the activity loss caused by Ami.Russian Foundation for Basic ResearchRevisión por pare