Functions of Herpesvirus-Encoded Homologs of the Cellular Ribonucleotide Reductase Large Subunit

Deoxyribonucleotides (dNTPs) are important for the efficient growth of DNA viruses. Therefore, many DNA viruses have strategies for the upregulation of cellular dNTP levels. Both α- and γ-herpesviruses encode functional homologs of cellular dNTP anabolic enzymes, including the class I ribonucleotide reductase (RNR) large (R1) and small (R2) subunits, whereas β-herpesviruses modulate host cells to induce genes that increase dNTP levels. Interestingly, β-herpesviruses still express the nonfunctional RNR R1 subunit. However, it is not clear why β-herpesviruses still carry inactive R1 homologs. Recently, the R1 homologs of herpesviruses have been shown to inhibit innate immune signaling pathways. In particular, both functional and nonfunctional R1 homologs target receptor-interacting protein kinase 1 (RIP1) and inhibit RIP1-mediated signaling pathways to promote viral replication. Here, we summarize recent findings on the activity of herpesviral R1 homologs and discuss their roles in the regulation of innate immune signaling pathways.

Clinical study of deoxyribonucleotidum for adjuvant treatment of pulmonary tuberculosis with hepatic lesion / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate of therapeutic efficacy of deoxyribouncleotidum on pulmonary tuberculosis.</p><p><b>METHODS</b>Eighty patients with pulmonary tuberculosis sustaining hepatic lesion after treatment with antituberculosis drugs were randomized into therapeutic group and control group. Patients in the control group received regular treatment and those in the therapeutic group had additional deoxyribouncleotidum injection.</p><p><b>RESULTS</b>ALT, AST, ALP and TBIL levels were significantly higher in the therapeutic group than in the control group 4 weeks after treatment. IgG, IgA, IgM levels, and CD3(+) and CD8(+) lymphocytes were significantly increased in the therapeutic group after treatment (P<0.05).</p><p><b>CONCLUSION</b>deoxyribouncleotidum can improve hepatic function and immunity in patients with pulmonary tuberculosis.</p>

Therapeutic effect of deoxyribonucleotidum on acute viral myocarditis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic efficacy of deoxyribonucleotidum in treatment of acute viral myocarditis.</p><p><b>METHODS</b>Eighty-eight patients with acute viral myocarditis were randomized equally into therapeutic group and control group. Patients in the control group were treated with routine treatment and those in the therapeutic group were given deoxyribonucleotidum in addition to routine treatment. After 4 weeks, the total efficacy rate and median time of symptom disappearance were compared between the two groups.</p><p><b>RESULTS</b>The total efficacy rate in the control and therapeutic groups was 79.54% and 95.45% (P=0.049), and the median time of symptom disappearance was 9.5 days and 6.5 days, respectively (P=0.035). Hypotension and mild dizziness were found in 2 patients in the therapeutic group without other severe side effects.</p><p><b>CONCLUSION</b>Deoxyribonucleotidum can improve the therapeutic effect for acute viral myocarditis.</p>

A Case of Cutaneous Manifestations Associated With Hydroxyurea Therapy / 대한피부과학회지

Hydroxyurea is an antitumor agent that has attained an important role in the management of myeloproliferative syndromes. Its mechanism of action is not fully understood, but it appears to affect DNA synthesis and genetic control of cell replication by inhibiting the conversion of ribonucleotides in deoxyribonucleotides. Cutaneous side effects such as xerosis, hyperpigmentation, nail changes, skin ulceration, alopecia, and palmoplantar keratoderma may occur, especially with long-term treatment. We report a case of 65-year-old chronic myelogenous leukemia(CML) patient showing various cutaneous manifestations after receiving long-term hydroxyurea therapy.

Indirect inhibition by antibiotics of nucleotide and deoxynucleotide biosynthesis in Plasmodium falciparum.

The effects of the antibiotics, doxycycline, azithromycin, ciprofloxacin and chloramphenicol, upon levels of nucleoside-5'-triphosphates (NTPs) and 2'-deoxynucleoside-5'-triphosphates (dNTPs) have been compared in the malarial parasite, Plasmodium falciparum, and in human CCRF-CEM leukemia cells. All 4 antibiotics had more severe effects upon levels of NTPs and dNTPs in P. falciparum compared with leukemia cells providing an explanation for their selective toxicity against malaria and their utility as antimalarial drugs. In bacteria, the first 3 drugs inhibit protein synthesis while ciprofloxacin inhibits topoisomerase II. The observed depletions of NTPs and dNTPs would be a secondary effect of the drug but may result in death of the parasite.