Video 1
HIV Replication 3D Medical Animation
HIV is the human immunodeficiency virus. If you have HIV, you have an infection that damages your immune system over time, and causes AIDS. AIDS stands for Acquired Immunodeficiency Syndrome. It is the final stage of an HIV infection, when your immune system is damaged and too weak to fight of ordinary infections. When foreign invaders, such as bacteria and viruses, get into your body, they can cause infections. These events activate your body’s defenses.
The white blood cells of your immune system are part of your body’s defenses. One type of white blood cell, called helper T lymphocytes or helper T cells, strengthen your immune system’s response to infection in two ways. First, helper T cells release chemicals that attract other white blood cells to the site of the infection. These additional white blood cells attack the invading bacteria or virus, as well as other infected cells. Second, helper T cells release chemicals that cause other white blood cells to multiply. These new white blood cells create markers called antibodies, which can identify the same foreign invader throughout your body. Antibody attached to the bacteria and virus, marking them as targets for your immune system to destroy them.
If you have HIV, it travels through your blood and other body fluids to infect and kill certain white blood cells. The virus enters helper T cells, which are the primary target. Once inside, the virus makes many copies of itself. As these virus particles are made, they leave the damaged helper T cell to infect other cells. The T cell loses its ability to protect the body from the ongoing infection and dies. In this way, HIV spreads and kills more of your helper T cells, weakening your immune system. As a result, other types of infections are able to take advantage of your body’s inability to defend itself. These infections are called opportunistic infections.
If you have an HIV infection, and one or more opportunistic infections, you have AIDS. Some of the common AIDS-related opportunistic infections are inflammation of the tissues covering your brain and spinal cord called meningitis, inflammation of your brain called encephalitis. Respiratory illnesses, such as pneumonia and tuberculosis. Intestinal illnesses, such as chronic diarrhea cause by infectious parasites. And cancers, such as Kaposi’s sarcoma and non-Hodgkin lymphoma.
HIV passed from person to person through infected body fluids. HIV can enter your body during unprotected sex, while sharing drug injection needles, during your own childbirth, while breastfeeding from your mother, or from contaminated blood or blood products. Although there is no cure for HIV, drugs called antiretroviral medications can reduce the amount of HIV in your body. One class of antiretroviral medication, called entry or fusion inhibitors, disrupts the HIV infection process by preventing the virus from attaching to your cells. Other classes of antiretroviral medications include reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors. These drugs prevent the creation, assembly and spread of new viruses. Your doctor may prescribe a combination of these drug classes, known as highly active antiretroviral therapy, or HAART.
Antiretroviral medication doesn’t completely remove HIV from your body, but slows it down enough to enable your immune system to fight infections. Regular blood tests will let your doctor know how effective your antiretroviral medication is in controlling HIV. If the number of helper T cells is high enough in your blood sample, your medication is working. Treatments for the opportunistic infections of AIDS are medications specific for each type of infection. For example, your doctor may prescribe antibiotics if you have pneumonia or tuberculosis.
To avoid getting or spreading an HIV infection, know your HIV status and your partner’s status by getting tested regularly. The most effective way to prevent HIV infection is to avoid vaginal and anal sex. When engaging in sexual activity, you will be less likely to contract HIV, if you only have sex with one uninfected partner or use latex condoms for protection. Avoid using injectable illegal drugs, or sharing drug needles, because the needles may have the virus on them. Avoid intoxication from drugs or alcohol, because you will be more likely to engage in unsafe sexual behavior.
Video 2
Targeting HIV replication
The replication of HIV-1 is a multi-stage process, each step is crucial to the successful replication and is therefore a potential target of antiretroviral drugs. Step one is infection of suitable host cells, such as CD4 positive T lymphocyte. Entry of the HIV into the cell requires the presence of certain receptors on the cell surface. CD4 receptors and coreceptors, such as CCR5 or CXCR4, these receptors interact with protein complexes which are embedded in the viral envelope.These complexes are composed of two glycoproteins, an extracellular GP120 and a transmembrane GP41. When HIV approaches the target cell, GP120 binds to the CD4 receptors, this process is termed attachment. It promotes further binding to a coreceptor，Coreceptor binding results in a conformational change in GP120，this allows GP41 to unfold and insert its hydrophobic terminus into the cell membrane. GP41 then folds back on itself. This draws the virus toward the cell and facilitates the fusion of their membranes.
The viral nuclear capsid enters the host cells and breaks open，releasing two viral RNA strands and three essential replication enzymes, integrase, protease and reverse transcriptase. Reverse transcriptase begins reverse transcription of the viral RNA, it has two catalytic domains, the ribonuclease H site and the polymerase active site. Here the single strand of viral RNA is transcribed into an RNA-DNA double helix. Ribonuclease H breaks down the RNA. The polymerase then completes the remaining DNA strand to form a DNA double helix. Now integrase goes into action, it cleaves the dinucleotide from each 3’ end of the DNA, creating two sticky ends. Integrase then transfers the DNA into the cell nucleus and facilitates its integration into the host cell genome. The host cell genome now contains the genetic information of HIV. Activation of the cell induces transcription of pro-viral DNA into messenger RNA. The viral messenger RNA migrates into the cytoplasm, where building blocks for a new virus are synthesized, some of them have to be processed by the viral protease.
Protease cleave the longer proteins into smaller core proteins, this step is crucial to create an infectious virus. Two viral RNA stands and replication enzymes then come together and core proteins assemble around them, forming the capsid. This immature viral particle leaves the cell, acquiring a new envelope of host and viral proteins. The virus matures and becomes ready to infect other cells.
HIV replicates billion of times per day, destroying the host immune cells and eventually causing disease progression. Drugs which interfere with the key steps of virus replication can stop this fatal process. Entry into the host cell can be blocked by fusion inhibitors for example. Inhibition of reverse transcriptase by nucleoside inhibitors or by non-nucleoside reverse transcription inhibitors is part of standards antiretroviral regimens. The action of integrase can be blocked. Protease inhibitors are also part of standard antiretroviral therapy. Each block step in viral replication is a step toward better control of HIV disease
