AIM:Study of antiviral activity of moraprenil phosphates (MPP) against herpes simplex type 1 virus (HSV1) in vitro and during experimental infection caused by HSV1 in mice.MATERIALS AND METHODS:Activity of MPP in vitro was tested by the ability to suppress formation of symplasts in VERO cells infected with HSV1, strain VR-3. A series of MPP that suppress virus-induced symplast-formation by 30 times was selected for in vivo experiments. Anti-viral activity of MPP in vivo was studied in HSV-1 infected mice after administration of either prophylaxis or therapy regimens.RESULTS:MPP at the dose of 20 microg/mice during s/c administration exhibited a pronounced prophylactic-therapeutic effect. Effectiveness of MPP during clinically evident herpes against the background of developing neurologic symptoms was demonstrated for the first time. Visual observation of the mice, that had received MPP as the first clinical symptoms of the disease appeared, has shown that against the background of preparation injection the clinical signs have ceased after 2 - 3 days and did not registered at least for the whole duration of the observation period (14 days).CONCLUSION:Active herpes infection is accompanied by the increase of FoxP3 expression in-thymus was shown. Possible mechanisms of anti-viral effect of MPP are discussed.

Исследована транскрипционная активность генов некоторых цитокинов (ЦТ)в головном мозге мышей при экспериментальной инфекции, вызвынной вирусом клещевого энцефалита (ВКЭ) после интрацеребрального заражения. Животные были разделены на группы с учетом выраженности признаков ВКЭ-инфекции. Показано, что ВКЭ-инфекция, сопровождающаяся неврологической симптоматикой, ассоциирована с высокими уровнями вирусной РНК в головном мозге. При этом регистрировались высокие уровни экспрессии генов провоспалительных ЦТ, что свидетельствует о выраженной воспалительной реакции, повреждающей головной мозг. Пероральное введение преднизолона достоверно снижало летальность инфицированных мышей. При и.ц. введении препарата на основе полипренилфосфата натрия (ППФ) наблюдалось снижение летальности с 67 % в группе животных, инфицированных ВКЭ, до 9 % в группе мышей, которым одновременно вводили ППФ и ВКЭ. При этом обнаружено, что и.ц. введение ППФ вызывает увеличение экспрессии гена IL6 в головном мозге в 5,4 раз по сравнению с контролем через 6 часов после введения, что, по-видимому, обусловливает активацию механизмов естественной резистентности и раннее подавление репродукции вируса. Эксперименты с антителами (АТ) к ВКЭ показали, что защитные свойства АТ проявляются лишь при условии их применения до или на ранних сроках после инфицирования. Введение АТ через 3–4 суток после интраперитонеального заражения мышей было неэффективно. Использование инъекций ППФ на поздних сроках относительно инфицирования также малоэффективно. По-видимому, это связано со значительным иммунопатогенным действием ВКЭ в этот период времени. В то же время введение ППФ с АТ оказывало защитное действие.

AIM:Study of macrophage migration inhibiting factor (MIF) effect after intracerebral administration on the course of experimental infection induced in mice by tick borne encephalitis virus (TEV), and study of sodium polyprenyl phosphate (PPP) and/or antibodies against MIF on the course of this infection against the background of MIF administration.MATERIALS AND METHODS:Phosprenil preparation was used as a source of PPP. PPP was administered intracerebrally. MIF--human recombinant (R&D, USA), mice--Balb/c line.RESULTS:In the sera of mice infected with TEV, MIF production stimulation was detected at days 8 through 10 after the infection--against the background of clinical signs presentation of tick borne encephalitis (TE). Administration of PPP to infected mice, on the contrary, resulted in MIF production suppression at the specified period. After administration of 20 ng of MIF to mice, lethality increased by 40% and average life span decreased by 2.3 days. Thus, MIF at high doses caused an increase of infection course severity, induced by TEV in mice, and administration of 60 microg of PPP resulted in the protection from infection in 100% of cases. Intracerebral administrationto mice of antibodies against MIF resulted in a decrease of lethality indicator up to 26% as compared with control and an increase of averagelife span by 5.5 days. During simultaneous administration into the brain of infected mice of MIF, PPP and antibodies against MIF, prevention of MIF-induced increase of TE course severity was registered.CONCLUSION:The data obtained allow to conclude that MIF may serve as an indicator of TE course severity, and possible prognostic indicator of meningo-encephalitic form development in humans.

Prospective anti-inflammatory activity of Phosprenyl (known veterinary drug with immunomodulating and antiviral activities) was studied using different in vitro and in vivo models. Phosprenyl exerted dose6dependent inhibitory effect on both 56lipoxigenase, and 156lipoxigenase activity. The inhibitory effect was observed even at a dose of 5 mcg/ml. Using yet another models of the hypostasis induced by the complete Freundt's adjuvant, or carraginan, we found that Phosprenyl exerted anti6inflammatory activity at both models of hypostasis, though it was weaker compared with indomethacin. In the in vivostudy Phosprenyl inoculation into mice infected with tick6born encephali6 tis virus (TBEV) led to decrease of the macrophage migration inhibitory factor (MIF) level in the blood serum, which was raised in the TBEV6infected mice. MIF inoculation into TBEV6infected mice led to the infection aggravation, while Phos6 prenyl inoculation into mice infected with TBEV, on the contrary, led to significant protection against the infection. Taking into account earlier established findings proving that Phosprenyl may function as a physiological counterregulator of MIF, a major proinflammatory cytokine, our data allow to conclude that Phosprenyl possesses anti6inflammatory activity