Case Definition For Epidemiological Surveillance
According to a study published in the Proceedings of the National Academy of Sciences in 2008, a team led by Robert Shafer at Stanford University School of Medicine discovered that the gray mouse lemur has an endogenouslentivirus in its genetic makeup. This suggests that lentiviruses have existed for at least 14 million years, much longer than the currently known existence of HIV. In addition, the time frame falls in the period when Madagascar was still connected to what is now the African continent the said lemurs later developed immunity to the virus strain and survived an era when the lentivirus was widespread among other mammals. The study was hailed as crucial, as it fills the blanks in the origin of the virus, as well as in its evolution, and could be important in the development of new antiviral drugs.
In 2010, researchers reported that SIV had infected monkeys in Bioko for at least 32,000 years. Previous to this time, it was thought that SIV infection in monkeys had happened over the past few hundred years. Scientists estimated that it would take a similar amount of time before humans adapted naturally to HIV infection in the way monkeys in Africa have adapted to SIV and not suffer any harm from the infection.
Targeting The Microglial Cells
Targeting all the HIV-1 reservoirs including the microglial cells in the brain is important in order to achieve either a sterilizing or a functional cure. Indeed, these cells are potential sources of HIV-1 reseeding in the blood. In addition, production of the virus in these cells has been associated with HIV-1 resistance and the development of HAND. However, targeting these cells which are located in anatomic and pharmacologic sanctuaries might be very challenging . Most importantly the access of drugs used in cART is limited by the blood brain barrier. Poor access of the drugs contributes to the persistence of HIV-1 in microglial cells . Another limitation is the existence of a residual neuroinflammation which is responsible for the occurrence of HAND in up to 50% of HIV-1 infected patients. A main concern is to prevent deleterious neuroinflammation associated with infected microglial cells . To date, three strategies are used to target infected microglial cells : the Shock and Kill strategy, the Block and Lock strategy, and gene therapy. We will discuss in the following section the principles of these three approaches and outline their limitations. Finally, we briefly discuss how these limitations can be circumvented and how to rationalize treatments aiming the eradication or reduction of the pool of latently infected microglial cells.
Mechanism Of Hiv Infection
). Once inside a CD4+ lymphocyte, the virus uses an enzyme called reverse transcriptase to make a copy of its RNA, but the copy is made as deoxyribonucleic acid that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells… read more ). HIV mutates easily at this point because reverse transcriptase is prone to making errors during the conversion of HIV RNA to DNA. These mutations make HIV more difficult to control because the many mutations increase the chance of producing HIV that can resist attacks by the persons immune system and/or antiretroviral drugs.
The HIV DNA copy is incorporated into the DNA of the infected lymphocyte. The lymphocytes own genetic machinery then reproduces the HIV. Eventually, the lymphocyte is destroyed. Each infected lymphocyte produces thousands of new viruses, which infect other lymphocytes and destroy them as well. Within a few days or weeks, the blood and genital fluids contain a very large amount of HIV, and the number of CD4+ lymphocytes may be reduced substantially. Because the amount of HIV in blood and genital fluids is so large so soon after HIV infection, newly infected people transmit HIV to other people very easily.
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Patients Cured Of Hiv Infection
The so-called “Berlin patient” has been potentially cured of HIV infection and has been off of treatment since 2006 with no detectable virus. This was achieved through two bone marrow transplants that replaced his immune system with a donor’s that did not have the CCR5 cell surface receptor, which is needed for some variants of HIV to enter a cell. Bone marrow transplants carry their own significant risks including potential death and was only attempted because it was necessary to treat a blood cancer he had. Attempts to replicate this have not been successful and given the risks, expense and rarity of CCR5 negative donors, bone marrow transplant is not seen as a mainstream option. It has inspired research into other methods to try to block CCR5 expression through gene therapy. A procedure zinc-finger nuclease-based gene knockout has been used in a Phase I trial of 12 humans and led to an increase in CD4 count and decrease in their viral load while off antiretroviral treatment. Attempt to reproduce this failed in 2016. Analysis of the failure showed that gene therapy only successfully treats 11-28% of cells, leaving the majority of CD4+ cells capable of being infected. The analysis found that only patients where less than 40% of cells were infected had reduced viral load. The Gene therapy was not effective if the native CD4+ cells remained. This is the main limitation which must be overcome for this treatment to become effective.
Homeless People And Intravenous Drug Users In New York
A volunteer social worker called Betty Williams, a Quaker who worked with the homeless in New York from the seventies and early eighties onwards, has talked about people at that time whose death would be labelled as “junkie flu” or “the dwindles”. In an interview for the Act Up Oral History Project in 2008, she said: “Of course, the horror stories came, mainly concerning women who were injection-drug users … who had PCP pneumonia , and were told that they just had bronchitis.” She continues: “I actually believe that AIDS kind of existed among this group of people first, because if you look back, there was something called junkie pneumonia, there was something called the dwindles that addicts got, and I think this was another early AIDS population way too helpless to ever do anything for themselves on their own behalf.”
Julia Epstein writes in her book Altered Conditions: Disease, Medicine and Storytelling that: “As we uncover more of the early history of HIV infection, it becomes clear that by at least the 1970s the virus was already making major inroads into the immune systems of a number of diverse populations in the United States and had for some time been causing devastation in several countries in Africa.”
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Hiv Assembly Budding And Maturation
Once the different viral components are built by the infected cell, they must be assembled and released at the plasma membrane. These components include two identical copies of the RNA genome, tRNAs from the host cell, and many copies of Env protein , Gag polyprotein, viral protease, RTs, and integrases.
The formation of a new HIV virus consists of three major stages:
1) Assembly. During this stage, different components are recruited to specific sites on the plasma membrane. Gag polyprotein is a key component that largely directs the assembly of an infectious particle. While one end of Gag binds to the RNA genome, the other end binds to the plasma membrane. Thousands of Gags assemble and become tightly packed during assembly.
2) Budding and Release. Packing of Gag polyproteins causes the plasma membrane to start to bulge out, eventually forming a spherical particle that resembles a lollipop. At this point, proteins known as ESCRTs are recruited and cut the plasma membrane neck, releasing the virus from the cell.
How Are T Cells Linked To Hiv And Aids
HIV enters its genetic information into helper T cells to make copies of itself. When this happens, the helper T cells die. This severely disrupts the immune response. Low levels of helper T cells mean killer T cells and other white blood cells do not receive as much information about pathogens in the body. As a result, disease-causing bacteria and viruses multiply with minimal detection.
When the amount of helper T cells falls below 200 cells/mm3 , a person may receive an AIDS diagnosis. But healthcare professionals will also take into account other variables such as overall white blood cell count and the percentage of lymphocytes.
AIDS is the most severe stage of HIV. When a person receives an AIDS diagnosis, their immune system is severely compromised, and they are at risk for opportunistic illnesses. The survival rate without treatment at this stage is typically
200 cells/mm3 , they will likely receive an AIDS diagnosis.
When a person has HIV, a healthcare professional will collect a blood sample and request a CD4 count. The CD4 count helps determine how many helper T cells a person has.
But when analyzing a CD4 count, healthcare professionals must take into account that:
- CD4 levels could be lower in the morning
- stress and fatigue may affect CD4 levels
- corticosteroid levels could increase or decrease CD4 levels
The CD4 count helps healthcare professionals monitor HIV progression and if the person is at risk for opportunistic illnesses.
100â150cells/mm3 after 1 year.
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How Is Aids Diagnosed
AIDS is the last and most severe stage of HIV infection. It is diagnosed if the results of your test show that you have:
- A CD4+ cell count of less than 200 cells per microliter of blood.
- A certain kind of infection called an opportunistic infection that is common in people who have weakened immune systems, such as Kaposi’s sarcoma or Pneumocystispneumonia.
What Is A Retrovirus
rather than as DNA DNA Genes are segments of deoxyribonucleic acid that contain the code for a specific protein that functions in one or more types of cells in the body. Chromosomes are structures within cells… read more .
When HIV enters a human cell, it releases its RNA, and an enzyme called reverse transcriptase makes a DNA copy of the HIV RNA. The resulting HIV DNA is integrated into the infected cells DNA. This process is the reverse of that used by human cells, which make an RNA copy of DNA. Thus, HIV is called a retrovirus, referring to the reversed process.
Other RNA viruses , unlike retroviruses, do not make DNA copies after they invade cells. They simply make RNA copies of their original RNA.
Each time an HIV-infected cell divides, it makes a new copy of the integrated HIV DNA as well as its own genes. The HIV DNA copy is either
HIV-1 originated in Central Africa during the first half of the 20th century when a closely related chimpanzee virus first infected people. The global spread of HIV-1 began in the late 1970s, and AIDS was first recognized in 1981.
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The Biology Of Microglial Cells
In conclusion, microglial cells fulfill several criteria of a brain reservoir. Most importantly they can subsist for a very long time in the brain and they can colonize the brain parenchyma. Contrary to other potential reservoirs in the brain, these cells divide slowly expanding the viral reservoirs in the brain and thus allowing virus persistence and reseeding of the blood. They are also involved in many functions including immune surveillance. As a consequence, any dysfunction of these cells might explain the occurrence of HAND.
Side Effects Of Hiv Treatment
Side effects of HIV medicine may vary from one drug to the next and from one person to another. Many of today’s HIV drugs make it possible to find a therapy that has few side effects for the individual.
HIV drug side effects may be judged troublesome or detected only through blood sample monitoring, which includes:
Some side effects may cause damage in the:
- Bone marrow
- Liver and pancreas
Side effects can occasionally increase the risk of cardiovascular disease and diabetes. Furthermore, HIV infection may increase the likelihood of developing such diseases. Routine checkups are thus required, both to monitor the action of the drug and identify any side effects.
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The Interaction Between Gp120 And Co
The interaction between CD4 and gp120 is conserved among all primate lentiviruses. Some of the amino acids on gp120 that form the CD4 binding site are variable, however, for these residues, the peptide backbone rather than their side chains are involved in contacting CD4. The co-receptor binding site on gp120 is not usually fully exposed until CD4 is bound. The variable V1/V2 loops are probably the main cover for the co-receptor binding site and these loops become repositioned when CD4 is bound. Mutations that expose the co-receptor binding site, therefore, confer a more CD4-independent phenotype.
The regions of gp120 implicated in the interaction with co-receptors are thought to involve the relatively conserved bridging sheet that lies between the protruding and variable V1/V2 and V3 loops, as well as some amino acids in V3 itself. The V3 loop has long been known to be a major determinant of cell tropism and now co-receptor use. Positively charged amino acids in V3 that confer a syncytium inducing phenotype correlate with CXCR4 use. The role of the V1/V2 loops in the co-receptor interaction is less clear since an HIV-1 mutant with V1/V2 deleted was infectious, while recombinant gp120 similarly deleted for V1 and V2 also bound co-receptors. When present, however, V1 and V2 influence both cell tropism and co-receptors used.
Through Blood Transfusions Or Organ Transplants
Currently, HIV infection is rarely transmitted through blood transfusions or organ transplants.
Since 1985 in most developed countries, all blood collected for transfusion is tested for HIV, and when possible, some blood products are treated with heat to eliminate the risk of HIV infection. The current risk of HIV infection from a single blood transfusion is estimated to be less than 1 in about 2 million in the United States. However, in many developing countries, blood and blood products are not screened for HIV or are not screened as stringently. There, the risk remains substantial.
HIV has been transmitted when organs from infected donors were unknowingly used as transplants. HIV transmission is unlikely to occur when corneas or certain specially treated tissues are transplanted.
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Quantification Of Jurkat Cell Growth
We here estimate the growth kinetics of Jurkat cells, which have been commonly used for HIV-1 studies, under the normal condition with the following mathematical model:
where the variable T is the number of Jurkat cells at time t and the parameters g and Tmax are the growth rate of the cells and the carrying capacity of the cell culture flask, respectively. Nonlinear least-squares regression was performed to fit Equation 4 to the time-course numbers of Jurkat cells in the normal condition. The fitted parameter values are listed in Supplementary file 2 and the model behavior using these best-fit parameter estimates is presented together with the data in Figure 2figure supplement 2.
What Happens Atthereverse Transcription And Integrationstage
Once inside the T-helper cell, HIV converts its genetic material into HIV DNA, a process called reverse transcription. The new HIV DNA then enters the nucleus of the host cell and takes control of it.
The types of ARVs that stop this stage of the lifecycle are called:
Integrase inhibitor drugs.
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How Does Hiv Spread
Human immunodeficiency virus is transmitted when virus-containing bodily fluids, such as blood, semen, vaginal fluid, anal secretions, or breast milk, enter the circulation of a person who does not have HIV, which can occur through:
- Unprotected anal or vaginal sex.
- Sharing injecting tools, particularly needles and syringes.
- Unsterile body piercing and tattoos.
- Unsterile surgical or dental treatments.
- The natural transmission of fluids from an HIV-positive mom to her kid during pregnancy, delivery, or lactation .
- Any wounds or sores in or around the mouth or genital area.
HIV cannot be transmitted through normal social interactions such as shaking hands, sharing a glass, sharing food or drink, or hugging and kissing. HIV is not transmitted through saliva, tears, sweat, feces, or urine. The patient cannot obtain HIV through a bug or animal bite or by sharing a bathroom with someone who has HIV.
In most workplaces and schools, people are not in danger of contracting HIV. However, there may be some danger if a job, education, or sport involves contact with blood and bodily fluids. Always practice basic hygiene, such as handwashing and safe management of bodily fluids such as blood spills.
What Are The Types Of Hiv Tests
There are three types of human immunodeficiency virus tests used to diagnose HIV infections, which are
- Antibody tests: These tests check for HIV antibodies in the blood or oral fluid.
- Antigen/antibody tests: These help to detect both HIV antibodies and antigens in the blood.
- Nucleic acid tests: These look for HIV in the blood.
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