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The region of the herpes simplex virus type 1 LAT gene that is colinear with the ICP34.5 gene is not involved in spontaneous reactivation. 总被引:4,自引:3,他引:1 下载免费PDF全文
G C Perng K Chokephaibulkit R L Thompson N M Sawtell S M Slanina H Ghiasi A B Nesburn S L Wechsler 《Journal of virology》1996,70(1):282-291
The goal of this report was to determine if the region of the LAT gene that is colinear with ICP34.5 (kb 6.2 to 7.1 of LAT) is involved in spontaneous reactivation of herpes simplex virus type 1. We inserted one copy of the ICP34.5 gene into the unique long region of a herpes simplex virus type 1 (strain McKrae) mutant lacking both copies of ICP34.5 (one in each viral long repeat) and the corresponding 917-nucleotide colinear portion of LAT (kb 6.2 to 7.1). Rabbits were ocularly infected with this mutant, and spontaneous reactivation relative to that for the wild-type virus and the original mutant was measured. As we previously reported, the original ICP34.5-deleted virus (d34.5) was significantly impaired for spontaneous reactivation and virulence (G. C. Perng, R. L. Thompson, N. M. Sawtell, W. E. Taylor, S. M. Slanina, H. Ghiasi, R. Kaiwar, A. B. Nesburn, and S. L. Wechsler, J. Virol. 69:3033-3041, 1995). In contrast, we report here that restoration of one copy of ICP34.5 at a distant location completely restored the wild-type level of in vivo spontaneous reactivation, despite retention of the deletion in LAT (spontaneous reactivation rate = 0.3 to 1.4% for the ICP34.5 deletion mutant, 7.7 to 19.6% for the wild type, and 9 to 16.1% for virus with one copy of ICP34.5). Thus, the 917-nucleotide region of LAT from kb 6.2 to 7.1 was not involved in the LAT function required for wild-type spontaneous reactivation. We also found that restoration of a single ICP34.5 gene in a novel location did not restore wild-type virulence (rabbit death rate = 0% [0 of 15] for the original ICP34.5 deletion mutant, 8% [2 of 24] for the single-copy IPC34.5 virus, and 52% [14 of 27] for wild-type virus; P < 0.001 for one versus two copies of ICP34.5). It is likely that either two gene doses of ICP34.5 or its location in the long repeat is essential for full functionality of ICP34.5's virulence function. Furthermore, the ability of the single-copy ICP34.5 virus to reactivate at wild-type levels despite being significantly less virulent than wild-type virus separates the spontaneous reactivation phenotype from the virulence phenotype. 相似文献
3.
An avirulent ICP34.5 deletion mutant of herpes simplex virus type 1 is capable of in vivo spontaneous reactivation. 总被引:6,自引:6,他引:0 下载免费PDF全文
G C Perng R L Thompson N M Sawtell W E Taylor S M Slanina H Ghiasi R Kaiwar A B Nesburn S L Wechsler 《Journal of virology》1995,69(5):3033-3041
The herpes simplex virus type 1 (HSV-1) ICP34.5 gene is a neurovirulence gene in mice. In addition, some ICP34.5 mutants have been reported to have a reduced efficiency of induced reactivation as measured by in vitro explantation of latently infected mouse ganglia. However, since spontaneous reactivation is almost nonexistent in mice, nothing has been reported on the effect of ICP34.5 mutants on spontaneous reactivation in vivo. To examine this, we have deleted both copies of the ICP34.5 neurovirulence gene from a strain of HSV-1 (McKrae) that has a high spontaneous reactivation rate in rabbits and used this mutant to infect rabbit eyes. All rabbits infected with the ICP34.5 mutant virus (d34.5) survived, even at challenge doses greater than 4 x 10(7) PFU per eye. In contrast, a 200-fold-lower challenge dose of 2 x 10(5) PFU per eye was lethal for approximately 50% of rabbits infected with either the wild-type McKrae parental virus or a rescued ICP34.5 mutant in which both copies of the ICP34.5 gene were restored. In mice, the 50% lethal dose of the ICP34.5 mutant was over 10(6) PFU, compared with a value of less than 10 PFU for the rescued virus. The ICP34.5 mutant was restricted for replication in rabbit and mouse eyes and mouse trigeminal ganglia in vivo. The spontaneous reactivation rate in rabbits for the mutant was 1.4% as determined by culturing tear films for the presence of reactivated virus. This was more than 10-fold lower than the spontaneous reactivation rate determined for the rescued virus (19.6%) and was highly significant (P < 0.0001, Fisher exact test). Southern analysis confirmed that the reactivated virus retained both copies of the ICP34.5 deletion. Thus, this report demonstrates that (i) the ICP34.5 gene, known to be a neurovirulence gene in mice, is also important for virulence in rabbits and (ii) in vivo spontaneous reactivation of HSV-1 in the rabbit ocular model, although reduced, can occur in the absence of the ICP34.5 gene. 相似文献
4.
Expression of herpes simplex virus type 1 glycoprotein I in baculovirus: preliminary biochemical characterization and protection studies. 下载免费PDF全文
We have constructed a recombinant baculovirus expressing the herpes simplex virus type 1 (HSV-1) glycoprotein I (gI). Sf9 cells infected with this recombinant virus synthesized gI-related polypeptides with apparent molecular sizes of 52 and 56 kDa. The recombinant gI appeared to be glycosylated, since it was susceptible to both tunicamycin and endoglycosidase H, and the expressed gI was transported to the surface of infected cells as judged by indirect immunofluorescence. Antibodies to the recombinant gI raised in mice neutralized HSV-1 infectivity. Finally, we show here for the first time that vaccination with gI can protect mice against HSV-1 challenge. 相似文献
5.
In vitro improvement of quail primordial germ cell expansion through activation of TGF‐beta signaling pathway 下载免费PDF全文
6.
Phosphodiesterase inhibitors (PDEIs) are a class of drugs that are widely used because of their various pharmacological properties including cardiotonic, vasodilator, smooth muscle relaxant, antidepressant, antithrombotic, bronchodilator, antiinflammatory and enhancer of cognitive function. In the recent years, interest in drugs of plant origin has been progressively increased. Some pharmacologically active substances that come from plants demonstrate PDEI activity. They mainly belong to alkaloids, flavonoids, and saponins. In this review, studies on herbal PDEI were reviewed and their possible therapeutic applications were discussed. Screening plants for PDE inhibitory activity may help to develop standardized phytotherapeutic products or find new sources for new lead structures with PDEI pharmacological activity. The studies discussed in this paper are mainly in vitro and for more reasonable and conclusive results, it is required to conduct in vivo and finally human and clinical tests. 相似文献
7.
Teymouri Babak Ghiasi Ghalehkandi Jamshid Hassanpour Shahin Aghdam-Shahryar Habib 《International journal of peptide research and therapeutics》2020,26(1):381-387
International Journal of Peptide Research and Therapeutics - The aim of the current study was to determine effect of in ovo feeding of vitamin B12 on hatchability, growth performance and blood... 相似文献
8.
Nemati Sara Pazoki Hossein Mohammad Rahimi Hanieh Asadzadeh Aghdaei Hamid Shahrokh Shabnam Baghaei Kaveh Mirjalali Hamed Zali Mohammad Reza 《Molecular biology reports》2021,48(10):7041-7047
Molecular Biology Reports - Autophagy process is an important defense mechanism against intracellular infection. This process plays a critical role in limiting the development of Toxoplasma gondii.... 相似文献
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Shirin Saberianpour Mohamad Hadi Saeed modaghegh Hamidreza Rahimi Mohammad Mahdi Kamyar 《Biophysical reviews》2021,13(1):139
Varicose veins are the most common vascular disease in humans. Veins have valves that help the blood return gradually to the heart without leaking blood. When these valves become weak, blood and fluid collect and pool by pressing against the walls of the veins, causing varicose veins. In the cardiovascular system, mechanical forces are important determinants of vascular homeostasis and pathological processes. Blood vessels are constantly exposed to a variety of hemodynamic forces, including shear stress and environmental strains caused by the blood flow. In varicose veins within the leg, venous blood pressure rises in the vein of the lower extremities due to prolonged standing, creating a peripheral tension in the vessel wall thereby causing mechanical stimulation of endothelial cells and vascular smooth muscle. Studies have shown that long-term increased exposure to vascular wall tension is associated with the overexpression of HIF-1α and HIF-2α and increased levels of MMP-2 and MMP-9, thereby reducing venous contraction and progressive venous dilatation, which is involved in the development of varicose veins. Following the expression of metalloproteinase, the expression of type 1 collagen increases, and the amount of type 3 collagen decreases. Therefore, collagen imbalance will cause the varicose veins to not stretch. Loss of structural proteins (type 3 collagen and elastin) in the vessel wall causes the loss of the biophysical properties of the varicose vein wall. This review article tries to elaborate on the effect of mechanical forces and sensors of these forces on the vascular wall in creating the mechanism of mechanosignaling, as well as the role of the onset of molecular signaling cascades in the pathology of varicose veins. 相似文献