Sunday, February 14, 2016

HIV contains copycat protein

HIV is a smart virus. It is also a copycat. It is smart because it actively evades detection so that it can cause AIDS by hijacking the body's immune cells. 
Researchers have deciphered how a small protein made by the Human Immunodeficiency Virus (HIV) that causes AIDS manipulates human genes to further its deadly agenda. 
Scientists have  long known that HIV  transforms ing them into HIV factories and killing other immune cells that normally fight disease. HIV also hides in cells and continues to undermine the host's immune system despite antiretroviral therapy that has improved the outlook of those with AIDS.
The findings, published in the online journal eLife, could aid in the search for new or improved treatments for patients with AIDS, or to the development of preventive strategies.
"We have identified the molecular mechanisms by which the Tat protein made by HIV interacts with the host cell to activate or repress several hundred human genes," said Dr. Iván D'Orso, Assistant Professor of Microbiology at UT Southwestern and senior author of the study. "The findings clearly suggest that blocking Tat activity may be of therapeutic value to HIV patients."
It has long been known that HIV causes AIDS by hijacking the body's immune cells, transforming them into HIV factories and killing other immune cells that normally fight disease. HIV also hides in cells and continues to undermine the host's immune system despite antiretroviral therapy that has improved the outlook of those with AIDS.
The latest data from the Centers for Disease Control and Prevention (CDC), in 2012, estimated 1.2 million Americans were living with HIV, including 156,300 whose infections had not been diagnosed. About 50,000 people in the U.S. are newly infected with HIV annually, the CDC projects. In 2013, the CDC estimated that over 26,000 Americans had the advanced form of HIV infection, AIDS.
Like all retroviruses, HIV has very few genes of its own and must take over the host's cellular machinery in order to propagate and spread throughout the body. Although the broad aspects of that cellular hijacking were known, the nuances remain to be explored, Dr. D'Orso said.
"We observed that HIV methodically and precisely manipulates the host's genes and cellular machinery. We also observed that HIV rewires cellular defensive pathways to benefit survival of the virus," he added.
The study provides insights into HIV's ability to survive despite antiretroviral therapy, findings that could lead to new therapeutic targets or ways to make current therapies more effective, he said.
"Our study indicates that this small viral protein, Tat, directly binds to about 400 human genes to generate an environment in which HIV can thrive. Then, this protein precisely turns off the body's immune defense. It is striking that such a small viral protein has such a large impact," Dr. D'Orso said. "The human genes and pathways that Tat manipulates correlate well with symptoms observed in these patients, such as immune system hyperactivation, then weakening, and accelerated aging," Dr. D'Orso said, describing the situation in which HIV infection leads to AIDS.
Italy's National Institute of Health in Rome recently completed a phase II clinical trial of an experimental vaccine that targets the Tat protein. That trial, which followed 87 HIV-positive patients for up to three years, reported that the vaccine was well-tolerated without significant side effects. However, it will take several years to determine if the vaccine works, Dr. D'Orso said.

Although someone can have HIV for years without showing symptoms, AIDS occurs when HIV blocks the body's ability to fight off illness. The person then becomes overrun by the opportunistic infections and specific cancers that are hallmarks of AIDS.

Zero tolerance for the scar of a lifetime

The day Folake, 13, was circumcised, she had no idea what was about to happen. She had gone to bed the previous evening only to be woken in the dead of the night by a loud bang on the door of the room where she and her 10-year-old sister slept.
The room was in inky darkness as the door crashed open and before Folake could move, she felt a large hand covering her mouth and nose while another strong hand lifted her off the bed and dragged her out of the room into the passage.
In shock and unable to protest or wriggle free, Folake  heard her sister screaming in the background, but under the pale, moon-lit night, as she was dragged out of the back door into the compound and onto the footpath leading to the main road, she  quickly became aware of some figures standing by the house.
She recognized one of those figures as her mother’s and made a vain attempt to call out to her. She was surprised that her mother made no move to rescue her from the assailant. Tears came to her eyes when she heard her mother whisper “Folake, you are going to be cut. It’s your turn.”
The rest of the events after that went by in a blur. Folake practically passed out as a result of the choking grip on her mouth and nose. When she came to, she found herself naked and spread-eagled on the floor in an unknown room.
A candle burned unsteadily nearby as she struggled hopelessly to get up, but was pinned onto floor by four women. A fifth woman knelt between her legs, bent over her lower abdomen with a razor blade in her right hand , urged her to stop struggling. “You won’t feel it. It's not going to be painful, the woman remarked.
But Folake felt it. As her flesh was being cut off, white-hot pain enveloped her entire being. The pain was more intense than she ever imagined. She bled a lot. For many days thereafter, she was in agony. She felt abused, violated and disenchanted.
Why, why? She kept asking. But there were no answers. She had gone through Type 3 form of Female Genital Mutilation and Cutting and did not know why.
Slowly she healed and time passed. She thought her ordeal was, but only became aware of how much she’d been affected psychologically and physiologically when she fell pregnant.
Folake was severely depressed and hated being vaginally examined. It was her worst nightmare.Her gynaecologist could not understand why she was so averse and so scared?
Folake did not know it, but her body was experiencing flashbacks - a reminder of what had happened to her when I was 13.
There are millions of girls and women like Folake that are victims of FGM/C. February 6, the International Day of Zero Tolerance for Female Genital Mutilation and Cutting, FGM/C, is  an awareness campaign to end the harmful practice that violates girls’ and women’s rights.
The World Health Organisation, WHO, describes female genital mutilation and comprising all procedures that involve altering or injuring the female genitalia for non-medical reasons. The practice is recognized internationally as a violation of the human rights of girls and women.  
In Nigeria and some other parts of the developing world, this practice has been described as reflecting deep-rooted inequality between the male and female sexes, and constituting an extreme form of discrimination against women and girls.
The practice also violates their rights to health, security and physical integrity, their right to be free from torture and cruel, inhuman or degrading treatment, and their right to life when the procedure results in death.
Although the practice of FGM cannot be justified by medical reasons, in many countries it is being executed more and more often by medical professionals, which constitutes ones of the greatest threats to the abandonment of the practice. 
Recent analysis of existing data shows that more than 18 percent of all girls and women who have been subjected to FGM have had the procedure performed by a health-care provider and in some countries this rate is as high as 74 percent. 
The situation of FGM/C in Nigeria according to NDHA 2013 reveals that due to its large population, Nigeria has the third highest absolute number of women and girls (19.9 million) who have undergone FGM/C worldwide (after Egypt and Ethiopia).
In it’s clinical description of FGM/C, the WHO describes it as comprising four types:  Type1: Clitoridectomy: partial or total removal of the clitoris and, in very rare cases, only the prepuce (the fold of skin surrounding the clitoris). Type2: Excision: partial or total removal of the clitoris and the labia minora, with or without excision of the labia; Type3: Infibulation: narrowing of the vaginal opening through the creation of a covering seal. Type IV (Unclassified): all other harmful procedures to the female genitalia for non-medical purposes, e.g. pricking, piercing, incising, scraping and cauterizing the genital area.
The National President, Inter-African Committee on FGM, Professor Modupe Onadeko, argues that the sensitisation against FGM/C  is now in the nurses’ curriculum at the University College Hospital, UCH, Ibadan, observes that we should not allow even one  girl to be mutilated again.
Onadeko  who argues that female circumcision is not the equivalent of male circumcision, said globally it is a violation of the girl child and the woman and has drawn criticism because of the hazards of health and complications.
“Female Genital Mutilation/Cutting has been with us for a long time. It is an accepted practice in so many cultures and it has been justified as to why it should go on, as the rites of the passage for preparing a girl to womanhood.
“I have researched and have not come across one good that comes out of FGM/C but there are numerous disadvantages.”   
Data from NDHS 2013, shows that 27 percent women 15-49 have been cut. It happens mainly before the 8th day or early teenage, during labour. An estimated 19.9 million Nigerian women have undergone FGM/C meaning that approximately 16 percent of the 125 million FGM/C survivors worldwide are Nigerians.
From left: Programme Officer, UNFPA Nigeria, Damilola 
Obinna; National President, Inter-African Committee on
 FGM, Professor Modupe Onadeko, and UNICEF Chief 
Communications Officer, Douane Porter. 
Programme Officer, UNFPA Nigeria, Damilola Obinna, notes that there are three sorrowful milestones for the girl child – the day of circumcision, the wedding night  (the fear of painful sexual intercourse) and  the day she would be having her baby. “We need to stop this practice.
Studies show that FGM/C is more prevalent in the southern zones than in the northern zones.  States with the highest prevalence include Osun (77 percent), Ebonyi (74 percent) , Ekiti (72 percent), Imo (68 percent ) and Oyo  (66 percent).
There is a Federal law outlawing the practice of FGM/C in Nigeria, the Violence Against Persons
(Prohibition) Act (VAPP), 2015, the practice continues.  
Eight states of the Federation have laws prohibiting FGM/C viz: Lagos, Osun, Ondo, Ekiti, Bayelsa, Edo, Cross River and Rivers. The Child Rights Act (CRA) 2004 also prohibits FGM/C
Reasons adduced for continuation of the practice range from tradition to preserving and continuing a set of values and rituals in a community, rite of passage from girlhood into womanhood, etc.
Child Protection Specialist, UNICEF, Maryam Enyiazu, FGM/C says is performed in Nigeria for cultural aesthetic reasons. In some communities, normal female genitals are considered ugly, unclean and unattractive unless they are subjected to FGM.
She says in some communities, it is believed that the clitoris contains powers strong enough to damage a man’s penis or to kill a baby during childbirth.
Solely focusing on the medical reasons has not helped. Medicalisation leads to legitimisation of the practice. But with collective support, FGM/C can be abandoned in this generation. That is the message today and every day.