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MiMl IP 3B LIFE/ (C)e C{iarlotte $ot Thursday, March 11,2004 HTV, rivals duel in cells Continued from page 4B — HIV’s preferred target — are infected with a mutant form of the virus that lacks Vif. That work — and that of laboratories following up on those findings — has uncov ered an unusual sequence of events that were the topic of much discussion last month at the 11th Retrovirus Conference, the annual mid winter AIDS meeting in the United States. It turns out that lympho cytes produce a substance that’s been given the unwieldy name APOBEC3G, It’s a member of a family of enzymes whose job is to edit RNA or DNA, the strands of genetic mater ial that constitute genes. The various APOBEC enzymes — there are nearly a dozen — make specific changes in a gene’s message. These are the equivalent of rewriting a word or two in a paragraph. That, in turn, alters the gene’s meaning in small but significant ways. This system of gene editing makes the storage of infor mation more economical. Genes whose messages dif fer by only a word or two don’t have to be spelled out separately in the cell’s genome. Instead, the ceU can store one version — and the minor variations can be cre ated by editing that tem plate once it’s transcribed, or copied. APOBEC3G, however, is an editor grown tired of wearing green eyeshades and thanklessly editing copy. APOBEC3G dreams of being a secret agent. It wants to turn its pencil into a lethal weapon. When an AIDS virus lack ing Vif infects a lymphocyte, molecules of APOBEC3G shadow the newly replicat ing virions. In a process that’s not fully understood, the enzyme sfips inside the viral envelope just before the envelope is sealed and the virion buds off from the cell. When that virion attaches to another cell and infects it, the material it unloads includes APOBEC3G. Transcribing and copying its genes into the cell’s DNA is an essential step in HIV’s rephcation. As the virus goes about this inside the newly infected cell, APOBEC3G goes to work, too. It edits — and edits and edits and edits. It edits the viral DNA transcript to a point where the message is such an unreadable mess that the ceU tears it up. 'This stops replication and breaks the chain of infection. This, at least, is what hap pens in APOBEC3G’s dreams. But it isn’t what happens in reality very often. 'That’s because HIV virions lacking Vif don’t exist in the wild — and for an obvious reason. They cannot make more of themselves when APOBEC3G is around. In reality, nearly all wild- type strains of HIV do have Vif. It is HIV’s own secret agent, evolved over time to neutralize APOBEC3G. Although many details of the mechanism are still rmdis- covered, Vif appears to work this way: As APOBEC3G trails a developing virion inside an infected ceU, 'Vif — which has been made in the cell from one of HIVs genes dur ing the replication process — hes in wait for it. As the edit ing enzyme is just about to sneak into the viral enve lope, W intercepts it. In a scene that would make the old Soviet KGB proud, this adventure-seek ing editor, clearly an ama teur in a world of profession als, is calmly led away irom the budding virion. Vif is quickly joined by other proteins named cuUin, elongin and ubiquitin. 'Ibgether they lead the hap less enzyme into a ceUular structure called a proteo- some — the Room "Where Very Bad Things Happen. There, quite literally, APOBEC3G is liquidated. How much this particular fight contributes to the body’s war of attrition against HIV is uncertain. “It has been obvious during the recent years that we come down [to defeat], but not without a fight,” Didier 'Trono of the University of Geneva told the scientists at the conference. “Even though we get outsmarted at the end, we give a good game to the virus.” Armed with these insights, scientists are hoping to change the outcome of the game. 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Citizens may send written comments via e-mail to telltransit@ci.charlotte.nc.us or mail them to: CATS, Attn: STS Public Comments 600 East Fourth Street, Oth floor Charlotte, NC 28202 For additional information, contact CATS at 704-336-RIDE or 866-779-CATS or visit us online at www.ridetransit.org. North Carolina Department of State Treasurer 325 NORTH SALISBURY STREET RALEIGH, NORTH CAROLINA 27603-1385 Having trouble with your taxes? Think you are entitled to a refund? You might be eligible for tax assistance through the Earned Income Tax Credit (EITC) If you earn between $11,000 and $35,000 a year, then you may qual ify to receive the EITC. Last year eligible taxpayers lost between $93 million and $176 mil lion of their own money because they did not claim federal taxes due back to them through the EITC. The failure to file for the EITC can cost a family an average of $1700 a year. Also, free tax services offered through this program can look at back taxes for up to three years to see if any money is owed back to you. To find out where the nearest free tax preparation session is or to see if you are eligible for the EITC, please visit www.nctreasurer.com Need a 529 college savings plan that gives you... tax-free earnings investment choices flexible contributions choice of any college in the country? You’ve got it with North Carolina’s National jCoHege Savings Program. You can enroll in the program directly or through your financial advisor. Begin building your child’s future today. Call for a free enrollment kit. North Carolina's^ National College' Savings Program 800-600-3453 WWW. C F N C. org/Savings College Foundation of North Carolina Helping You Plan. Apply, and Pay for College S) College Foundation, Inc. 2004
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