Extended Data Fig 5 Vbp Sensitizes The Card8 Inflammasome To Hiv
a, VbP overcomes reduced RPV killing efficacy by human serum. Dose response curves for killing of HIV-1-infected CD4+ T cells treated with RPV or combo with or without the presence of 50% human serum. Zero values of RPV were plotted at 0.1nM to allow for log transformation. Error bars show mean values with SEM . be, Time course treatment of three donors of HIV-1 infected primary CD4+ T cells or THP-1 cells . Cells were treated with DMSO, EFV , VbP , or combo. Fold change enhancement of combination treatment in comparison to EFV alone treatment was shown in and .
Immune Selection Pressure And Viral Escape
The impact of CTL selection pressure is readily observed by sequencing autologous virus, which undergoes rapid immune-driven evolution in vivo following acute infection . New approaches involving single genome amplification techniques have shown clear evidence of CTL escape within 2532 days of infection, around the time of peak viremia following acute infection, and before full seroconversion . Indeed, deep sequencing has revealed that the virus explores multiple pathways to escape before going to fixation, indicating that there are constraints on HIV evolution that appear to be caused by imposed fitness alterations . The pathways to immune escape appear limited, as shown by studies of genetically identical twins infected by the same virus as adults through shared injection drug use, in whom the earliest targeted epitopes, kinetics of escape and earliest escape variants that arose were strikingly similar , despite differences in T-cell receptor usage .
Future Directions: Toward A Unified Explanation For Hiv Pathogenesis
A unified view of HIV pathogenesis is emerging, but there remain many unknowns, and a better understanding will undoubtedly require an integrated analysis of innate and adaptive immune responses, host genetics, and viral genetics. Although both viral load and CD4+ cell count predict disease progression, we remain convinced that the adaptive immunologic response is also predictive of the subsequent course. Clear signals are there: CD8+ T cells are associated with initial control, depletion of these cells in animal models of AIDS leads to an increase in viremia, virus is evolving to escape detection by CTLs, specific functions mediated by CD8+ T cells have demonstrable antiviral effects in vivo, the effect of HLA far outweighs any other genetic factors, CD8+ and CD4+ T-cell dysfunction is associated with lack of viral control, and immune-induced mutations reduce viral fitness and likely contribute to the antiviral efficacy of the CD8+ T-cell response. But important questions remain, and in particular questions regarding the actual functional profile of CD8+ T cells that might lead to long-term control of HIV, or prevention of disseminated infection. And the extent to which such data will be important to vaccine design remains unclearalthough animal models suggest that CD8+ T cells may be able to prevent progressive systemic dissemination of infection and even reduce the level of virus to barely detectable levels .
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Signal Transduction Through Ccr5 And Cxcr4
CCR5 and CXCR4 are both members of the seven-transmembrane-spanning family of heterotrimeric GPCRs. This family of proteins is characterized by an extracellular amino-terminal domain, seven membrane-spanning domains that form three extracellular and three intracellular loops, and a cytoplasmic tail domain. The amino terminus and three ECLs together form the binding pocket for the cognate chemokines, which appear to attach to their receptor and transmit signals in a two-site binding process . The intracellular loops and cytoplasmic tail bind to the heterotrimeric G proteins that in turn mediate effector functions.
A second series of experiments from Harmon and colleagues showed that HIV also signals through the Gq subunit, resulting in phospholipase C and Rac activation. Rac and the tyrosine kinase Abl then become linked to the Wave2 complex through the adapter proteins Tiam-1 and IRSp53, promoting Arp2/3-dependent actin nucleation and polymerization. Blocking activation of the Wave2 complex with small interfering RNAs or Abl kinase inhibitors arrested HIV entry at the hemifusion stage. Together, these experiments suggest a critical role for envelope-coreceptor signaling-induced actin remodeling during HIV entry, particularly in the case of resting CD4+ T cells.
Home Test Kits For Hiv
A home test kit for HIV has been approved by the U.S. Food and Drug Administration . For the test, you rub your gums with a swab supplied by the kit. Then you place the swab into a vial of liquid. The test strip on the swab indicates if you have HIV or not.
Another type of test kit for HIV is a home blood test kit. This type of kit provides instructions and materials for collecting a small blood sample by sticking your finger with a lancet. The blood is placed onto a special card that is then sent to a lab for analysis. You get the results over the phone using an anonymous code number. Counseling is also available over the phone for people who use the test kit.
If the results from a home test kit show that you have an HIV infection, talk with a doctor.
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Human Immunodeficiency Virus Infection
, MD, MAS, University of California, San Diego School of Medicine
HIV is transmitted through close contact with a body fluid that contains the virus or cells infected with the virus .
HIV destroys certain types of white blood cells, weakening the bodys defenses against infections and cancers.
When people are first infected, symptoms of fever, rashes, swollen lymph nodes, and fatigue may last a few days to several weeks.
Many infected people remain well for more than a decade.
About half of untreated people become ill and develop AIDS, defined by the presence of serious infections and cancers, within about 10 years.
Eventually, most untreated people develop AIDS.
Blood tests to check for HIV antibody and to measure the amount of HIV virus can confirm the diagnosis.
HIV drugs two, three, or more taken togethercan stop HIV from reproducing, strengthen the immune system, and thus make people less susceptible to infection, but the drugs cannot eliminate HIV, which persists in an inactive form.
HIV infections may be caused by one of two retroviruses, HIV-1 or HIV-2. HIV-1 causes most HIV infections worldwide, but HIV-2 causes many HIV infections in West Africa.
Diagnosis Of Hiv Infection
Tests to detect antibodies to the HIV virus in a sample of blood or saliva
Tests to detect HIV RNA in a sample of blood
Early diagnosis of HIV infection is important because it makes early treatment possible. Early treatment enables infected people to live longer, be healthier, and be less likely to transmit HIV to other people.
Doctors usually ask about risk factors for HIV infection Transmission of HIV Infection Human immunodeficiency virus infection is a viral infection that progressively destroys certain white blood cells and can cause acquired immunodeficiency syndrome . HIV is transmitted… read more and about symptoms .
Doctors also do a complete physical examination to check for signs of opportunistic infections, such as swollen lymph nodes and white patches inside the mouth , and for signs of Kaposi sarcoma of the skin or mouth.
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Hiv Prevention And Treatment
If a person is HIV positive, there are treatment options to keep them healthy and prevent them from transmitting it. Thankfully, with proper treatment for HIV, people can live long, healthy lives by keeping their viral load under control in Stage 2.
HIV treatment drugs suppress a persons viral load or the number of HIV cells in the body. Doctors will monitor the cell count and when it falls an undetectable range, they are considered to be non-transmittable.
Scientific research has proven that a person cannot transmit HIV to another partner if their viral load is undetectable. This is commonly which stands for undetectable = untransmittable.
Of course, the best way to stop HIV transmission is to understand how to protect yourself and others from exposure. Using condoms and avoiding sharing needles is effective but taking PrEP can provide the greatest protection even if you are accidentally exposed.
PrEP is a medication prescribed by a doctor which can lower the risk of HIV transmission significantly. This drug stops HIV from being able to reproduce in the body. So, it can be taken before exposure and stop HIV transmission.
If a person has knowingly been exposed to HIV and is not currently on PrEP or has missed numerous doses, then they will be prescribed PEP. This is a medication regimen of HIV prevention drugs that must be administered with 72 hours of exposure. This can stop HIV from reproducing and diminish a persons viral load.
What Questions Should I Ask My Doctor
- Am I at high risk for HIV?
- What can I do to reduce my risk of HIV?
- How can I make sure I take my medications correctly?
- What can I do to protect myself from other illnesses?
- How can prevent the spread of HIV?
- What do my test results mean?
- What do my blood counts mean?
- What vaccinations should I get?
A note from Cleveland Clinic
Treatments have come a long way since the height of the AIDS epidemic. You have the best chance of living a long life if youre diagnosed early and are able to get on and stick with ART medications. People living with HIV today are able to work, have active social lives and families, and pursue fulfilling relationships. In fact, this can have a positive impact on your well-being.
While weve come a long way with treatments, unfortunately, social stigmas around HIV still persist. In addition to the feelings of fear and uncertainty a new diagnosis can bring, you may wonder how those around you will respond. If youre hesitant to get tested or get treatment, or if you just arent sure what your next steps are, you can reach out to a community organization that specializes in HIV. Remember that you are deserving of support, compassion and high-quality healthcare.
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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.
What Does Hiv Do To The Immune System
The term HIV is often synonymously used with AIDS. However, it is important to understand the distinctions between these medical terms. Sadly, many people are quite unfamiliar with the symptoms of HIV, how HIV is transmitted, and the progression of HIV to AIDS. This lack of knowledge puts them at a high risk of HIV transmission.
First, lets explain what HIV is.
People can go many years without knowing that they have HIV. In fact, it is estimated that about 1 in 7 people are HIV positive but are unaware as they have never been tested. However, over ten years or so, their immune system will become extremely compromised until they develop AIDS unless they take HIV treatment drugs.
So, how does this happen and why does HIV attack the immune system? Lets dive in.
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How Can I Know If I Have Hiv
You cant tell if someone has HIV just by looking at them, and you may not have any symptoms if youre infected by HIV. The only way to know if you have HIV is to take an HIV test.
Since nearly 1 out of 7 people with HIV dont know it, the U.S. Centers for Disease Control & Prevention recommends screening people between the ages of 13 to 64 at least once as part of routine healthcare. This test is voluntary and confidential.
What The Results Mean
A normal CD4 count is from 500 to 1,400 cells per cubic millimeter of blood. CD4 counts go down over time if you do not take ART.
At levels below 200 cells per cubic millimeter, you are more likely to get to a wide variety of OIs, many of which can be deadly.
Your CD4 levels behave differently depending on your stage of HIV:
Stage 1: Acute HIV Infection. HIV is reproducing in large amounts and destroying CD4 cells. Thatâs why CD4 levels typically fall quickly at first. Then, as your immune system responds, your viral load begins to fall and your CD4 levels start to rise again. But they might not return to pre-infection levels.
Stage 2: Chronic HIV Infection. HIV is still active but reproduces much more slowly. ART treatment can keep you in this stage for many decades. This can help maintain CD4 at healthy levels, sometimes indefinitely. If this period starts to head toward stage 3, your viral load goes up and CD4 levels go down.
Stage 3: AIDS. Your immune system is damaged badly enough to allow opportunistic infections of different types. Your doctor might diagnose AIDS because of these. But your doctor can also diagnose this stage by CD4 levels. Once they get below 200, most doctors will diagnose AIDS.
Anyone who is HIV-positive should take antiretroviral therapy medications regardless of their CD4 count and whether or not they have symptoms. When your treatment is working, your CD4 count should stay steady or go up.
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Where Does Virus Entry Occur
The entry of viruses into cells is controlled in both time and space, with these parameters being regulated by host cell factors that serve to unlock the membrane fusion potential of viral membrane proteins. Many viruses require delivery by the host cell into an acidic, intracellular compartment where low pH triggers membrane-fusion-inducing conformational changes . HIV entry does not require low pH instead it is triggered by receptor engagement . The fact that HIV does not require low pH for cellular entry does not imply that fusion occurs at the cell surface. In fact, no spatial information is provided by the triggering mechanism. Despite this, it was often assumed that HIV fuses at the cell surface owing to several observations . First, Env expression on the cell surface can mediate cell-to-cell fusion, indicating not only that Env is the only viral membrane protein needed to elicit fusion but that low pH is clearly not required. Second, very early studies on HIV entry showed that lysomotropic agents, which increase endosomal pH, do not inhibit HIV infection . Third, inhibiting endocytosis of CD4 in cell lines by mutating its cytoplasmic domain does not affect HIV infection . Together, these studies show that HIV entry is not pH dependent, but they provide no definitive information as to whether fusion occurs at the cell surface or from within endocytic vesicles, albeit in a pH-independent fashion.
What Are The Factors That Affect Disease Progression
The most important factor affecting HIV progression is the ability to achieve viral suppression. Taking antiretroviral therapy regularly helps many people slow the progression of HIV and reach viral suppression.
However, a variety of factors affect HIV progression, and some people progress through the phases of HIV more quickly than others.
Factors that affect HIV progression can include:
- Ability to achieve viral suppression. Whether someone can take their antiretroviral medications and achieve viral suppression is the most important factor by far.
- Age when symptoms start. Being older can result in faster progression of HIV.
- Health before treatment. If a person had other diseases, such as tuberculosis, hepatitis C, or other sexually transmitted diseases , it can affect their overall health.
- Timing of diagnosis. Another important factor is how soon a person was diagnosed after they contracted HIV. The longer between their diagnosis and treatment, the more time the disease has to progress unchecked.
- Lifestyle. Practicing an unhealthy lifestyle, such as having a poor diet and experiencing severe stress, can cause HIV to progress more quickly.
- Genetic history. Some people seem to progress more quickly through their disease given their genetic makeup.
Some factors can delay or slow the progression of HIV. These include:
Living a healthy lifestyle and seeing a healthcare provider regularly can make a big difference in a persons overall health.
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Testing Positive For Hiv
If you test positive, your doctor will complete a medical history and physical exam.
He or she may order several lab tests to check your overall health, including:
- A complete blood count , to identify the numbers and types of cells in your blood.
- A chemistry screen, to measure the blood levels of certain substances and to see how well your liver and kidneys are working.
Other tests may be done to check for current or past infections that may become worse because of HIV. You may be tested for:
Hiv Is An Infection That Can Lead To Aids
HIV stands for Human Immunodeficiency Virus. Its a virus that breaks down certain cells in your immune system . When HIV damages your immune system, its easier to get really sick and even die from infections that your body could normally fight off.
About 1.1 million people in the U.S. are living with HIV, and more than 38,000 new infections happen every year. Most people with HIV dont have any symptoms for many years and feel totally fine, so they might not even know they have it.
Once you have HIV, the virus stays in your body for life. Theres no cure for HIV, but medicines can help you stay healthy. HIV medicine lowers or even stops your chances of spreading the virus to other people. Studies show that using HIV treatment as directed can lower the amount of HIV in your blood so much that it might not even show up on a test when this happens, you cant transmit HIV through sex.Treatment is really important . Without treatment, HIV can lead to AIDS. But with medicine, people with HIV can live long, healthy lives and stop the spread of HIV to others.