Tuesday, October 4, 2022

How Does Hiv Enter The Cell

Hiv Invasion Of Immune Cells

How HIV infects us: Mucous membranes, dendritic cells, and lymph nodes | Khan Academy

HIV infects T cells via high-affinity interaction between the virion envelope glycoprotein and the CD4 molecule. The infection of T cells is assisted by the T-cell co-receptor called CXCR4 while HIV infects monocytes by interacting with CCR5 co-receptor . As illustrated in Figure 2, after gp120 binds to CD4 on the T cell . Nucleocapsids containing viral genome and enzymes enters the target cell . Following the release of viral genome and enzymes from the core protein, viral reverse transcriptase catalyses reverse transcription of ssRNA to form RNA-DNA hybrids . To yield HIV dsDNA the viral RNA template is partially degraded by ribonuclease H and the second DNA strand is synthesized . The viral dsDNA is translocated into the nucleus and integrated into the host genome by the viral integrase enzyme . Transcription factors transcribe the proviral DNA into genomic ssRNA , which is exported to cytoplasm . In the cytoplasm, host-cell ribosomes catalyse synthesis of viral precursor proteins . The viral precursor proteins are cleaved into viral proteins by viral proteases . HIV ssRNA and proteins assemble beneath the host-cell plasma membrane forming virion buds from it . Maturation occurs either in the forming buds or after budding from the host cell . During maturation, HIV proteases cleave the poly-proteins into individual functional HIV proteins. The mature virions are able to infect another host cell.

Figure 1. Figure 2.

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.

Strategies For Preventing The Transmission Of Hiv

  • Abstain from sexual activity.

  • Use a latex condom for each act of intercourse with an infected partner or a partner whose HIV status is unknown .

  • For men engaging in oral sex, withdraw before ejaculation.

  • For men, get circumcised .

  • For newly monogamous couples, get tested for HIV infection and other sexually transmitted diseases before engaging in unprotected sexual intercourse.

  • Never share needles or syringes.

  • Wear rubber gloves when touching body fluids of another person .

  • If accidentally exposed to fluids containing HIV , seek treatment with antiretroviral drugs to prevent infection.

Condoms made of latex provide good protection against HIV , but they are not foolproof. Oil-based lubricants should not be used because they may dissolve latex, reducing the condom’s effectiveness.

Other measures can help. For men, circumcision, an inexpensive, safe procedure, reduces the risk of becoming infected during vaginal intercourse with an infected woman by about half. Whether circumcision reduces the risk of HIV infection in other circumstances is unclear. Because circumcision provides only partial protection against HIV infection, people should also use other measures to prevent HIV infection. For example, if either partner has a sexually transmitted disease or HIV infection, it should be treated, and condoms should be used correctly and consistently.

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Why Does The Immune System Fail To Fight The Hiv Virus

There are various reasons which can contribute to the failure of the immune system to control HIV infection and prevent AIDS development. By infecting CD4+ T cells, HIV is able to replicate predominantly in activated T cells and paralyse one of the main components of adaptive immune system. HIV can also establish latent infection in CD4+ T cells and remain invisible to CD8+ T cells and therefore replication can occur later in the infection and generate new virions. Antigenic mutation within the T-cell epitopes can affect the binding capacity of MHC molecules to the viral peptides, resulting in the inability of the TCRs to recognise the MHC-peptide complex. Finally, HIV is able to hide from anti-HIV antibodies by expressing non-immunogenic glycans on key antibody epitopes.

Presence Of Multinucleated Giant Cells In Infected Tissues

Basic Virus Cell Diagram

The mechanism of T-cell syncytia formation has been largely documented in vitro and discussed for its in vivo relevance. Nonetheless, processes of cellcell fusion for HIV-1 infection and dissemination are not restricted to T cells. Some studies showed that infected multinucleated macrophages, as well as multinucleated DCs, could be found in different tissues in vivo in HIV-1-infected patients . The presence of HIV-1-infected multinucleated syncytia expressing specific DC markers was found at the surface of the nasopharyngeal tonsils of HIV-1-infected patients and reported 20 years ago . The same group reported that infected T cells could fuse in vitro with skin-derived DCs , thus leading to multinucleated cell formation between T cells and DCs. Similarly, multinucleated giant HIV-1-infected macrophages have been found in vivo during infection in several different tissues, including lymph nodes, spleen, lungs, genital, and digestive tracts, and the central nervous system . While several groups showed the presence of infected multinucleated macrophages in tissues, and more specifically in the brain of HIV-1-infected patients and SIV-infected monkeys, the cellular and molecular mechanisms related to their formation remained poorly investigated, with only one in vitro study demonstrating a role for the HIV-1 auxiliary protein Nef in the formation of multinucleated macrophages .

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How Is Hiv Treated

Treatments for HIV typically involve antiretroviral therapy. This isnt a specific regimen, but instead a combination of three or four drugs. The U.S. Food and Drug Administration has currently approved nearly 50 different medications to treat HIV.

Antiretroviral therapy works to prevent the virus from copying itself. This maintains immunity levels while slowing the progression of HIV.

Before prescribing medication, a healthcare provider will take the following factors into consideration:

  • a persons health history
  • the levels of the virus in the blood

HIV doesnt cause a lot of outward or noticeable symptoms until the disease has progressed. For this reason, its important to understand how HIV is transmitted and the ways to prevent transmission.

HIV can be transmitted by:

  • having sex, including oral, vaginal, and anal sex
  • sharing needles, including tattoo needles, needles used for body piercing, and needles used for injecting drugs
  • coming into contact with body fluids, such as semen, vaginal fluid, blood, and breast milk

HIV is not transmitted by:

  • breathing the same air as a person living with HIV
  • getting bitten by a mosquito or other biting insect
  • hugging, holding hands with, kissing, or touching a person living with HIV
  • touching a door handle or toilet seat thats been used by an HIV-positive person

Keeping this in mind, some of the ways a person can prevent HIV include:

Symptoms can take years to appear, which is why its so important to get tested regularly.

Therapies Targeted At Hiv Receptors

The identification of HIV co-receptors has provided an exciting new therapeutic opportunity. Drugs aimed at blocking envelope interactions with both CCR5 and CXCR4 are being developed. CCR5 is an excellent target for therapy since individuals homozygous for the 32 base pair deletion in CCR5 are effectively CCR5-negative but healthy. Agents that specifically block the natural CCR5 receptor activity should, therefore , not be harmful. There has been much debate about whether inhibitors of R5 strains will select for the more pathogenic X4 variants, or for variants that exploit alternative co-receptors. Extensive evidence that shows 32 CCR5 heterozygotes progress more slowly to AIDS bodes well for CCR5 inhibitors that will also decrease the level of functional CCR5 for HIV infection. One report, however, suggested caution and showed that CXCR4-using viruses may be present more frequently in 32 CCR5 heterozygotes Moreover, variation in use of CCR5 by different R5 strains may mean that variant viruses will emerge that escape CCR5 inhibitors but still use CCR5 as a co-receptor. Regardless, co-receptor drugs will be used in combination with agents that target other events in the virus life cycle, e.g. RT or protease inhibitors. In these situations, virus replication should be driven down to very low levels minimizing the chances of accruing mutations that confer escape from CCR5 inhibitors.

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Entry Via Membrane Fusion

The most well-known example is through membrane fusion. In a number of viruses with a viral envelope, viral receptors attach to the receptors on the surface of the cell and secondary receptors may be present to initiate the puncture of the membrane or fusion with the host cell. Following attachment, the viral envelope fuses with the host cell membrane, causing the virus to enter. Viruses that enter a cell in this manner included HIV, KSHV and herpes simplex virus.

How Does Chronic Hiv Affect The Body

How the HIV virus enters the cell xvid

The chronic HIV stage is known as the latent or asymptomatic stage. During this stage, a person usually wont have as many symptoms as they did during the acute phase. This is because the virus doesnt multiply as quickly.

However, a person can still transmit HIV if the virus is left untreated and they continue to have a detectable viral load. Without treatment, the chronic HIV stage can last for many years before advancing to AIDS.

Advances in antiretroviral treatments have significantly improved the outlook for people living with HIV. With proper treatment, many people who are HIV-positive are able to achieve viral suppression and live long, healthy lives. Learn more about HIV and life expectancy.

A normal CD4 count ranges from approximately 500 to 1,600 cells per cubic millimeter of blood in healthy adults, according to HIV.gov.

A person receives an AIDS diagnosis when they have a CD4 count of fewer than 200 cells/mm3.

A person may also receive an AIDS diagnosis if theyve had an opportunistic infection or another AIDS-defining condition.

People with AIDS are vulnerable to opportunistic infections and common infections that may include tuberculosis, toxoplasmosis, and pneumonia.

People with weakened immune systems are also more susceptible to certain types of cancer, such as lymphoma and cervical cancer.

The survival rate for people with AIDS varies depending on treatment and other factors.

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Integrationhiv Becomes Part Of The Infected Cell

At this point, a second viral enzyme called integrase inserts the newly converted viral DNA into the cells own DNA. With the viral DNA integrated into the DNA of the cell, the virus has become part of the cell. This process has been compared to putting a bug in a computer software program. Drugs that stop, or inhibit, HIV from integrating into human cells are called integrase inhibitors.

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.

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Simplified Life Cycle Of The Human Immunodeficiency Virus

Like all viruses, human immunodeficiency virus reproduces using the genetic machinery of the cell it infects, usually a CD4+ lymphocyte.

  • HIV first attaches to and penetrates its target cell.

  • HIV releases RNA, the genetic code of the virus, into the cell. For the virus to replicate, its RNA must be converted to DNA. The RNA is converted by an enzyme called reverse transcriptase . HIV mutates easily at this point because reverse transcriptase is prone to errors during the conversion of viral RNA to DNA.

  • The viral DNA enters the cells nucleus.

  • With the help of an enzyme called integrase , the viral DNA becomes integrated with the cells DNA.

  • The DNA of the infected cell now produces viral RNA as well as proteins that are needed to assemble a new HIV.

  • A new virus is assembled from RNA and short pieces of protein.

  • The virus pushes through the membrane of the cell, wrapping itself in a fragment of the cell membrane and pinching off from the infected cell.

  • To be able to infect other cells, the budded virus must mature. It becomes mature when another HIV enzyme cuts structural proteins in the virus, causing them to rearrange.

Drugs used to treat HIV infection were developed based on the life cycle of HIV. These drugs inhibit the three enzymes that the virus uses to replicate or to attach to and enter cells.

HIV also infects other cells, such as cells in the skin, brain, genital tract, heart, and kidneys, causing disease in those organs.

Hiv Variation In Different Tissues

Human Immunodeficiency Virus a Student Update

Envelope/co-receptor interactions may also influence early post-entry events in some cell types favouring some strains over others. For instance, the observations that both M-tropic and T-tropic SIVMAC strains enter macrophages, while only M-tropic envelopes signal via CCR5 has raised the possibility that co-receptor signalling events induced by a virus entering at the cell surface may be a requirement for replication in some cell types. Signalling during virus entry, however, is controversial and recent data showing that increased expression of CCR5 on the surface of macrophages fully rescues T-tropic SIV replication probably argue against, in this instance.

Thus different cell types in distinct environments will select for or against particular R5 viruses or quasispecies however, the extent this happens and its impact on pathogenesis is unclear.

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Interval Of Mild Or No Symptoms

After the first symptoms disappear, most people, even without treatment, have no symptoms or only occasionally have a few mild symptoms. This interval of few or no symptoms may last from 2 to 15 years. The symptoms that most commonly occur during this interval include the following:

  • Swollen lymph nodes, felt as small, painless lumps in the neck, under the arms, or in the groin

  • White patches in the mouth due to candidiasis

  • Anemia

Some people progressively lose weight and have a mild fever or diarrhea.

These symptoms may result from HIV infection or from opportunistic infections that develop because HIV has weakened the immune system.

Innate Immune Response To Hiv

Innate immune cells are the first line of defence which HIV encounters upon entry to the body.

Macrophages. Tissue macrophages are one of the target cells for HIV. These macrophages harbour the virus and are known to be the source of viral proteins. However, the infected macrophages are shown to lose their ability to ingest and kill foreign microbes and present antigen to T cells. This could have a major contribution in overall immune dysfunction caused by HIV infection.

Dendritic cells . DCs are large cells with dendritic cytoplasmic extensions. These cells present processed antigens to T lymphocytes in lymph nodes. Epidermal DCs, expressing CD1a and Birbeck granules, are probably among the first immune cells to combat HIV at the mucosal surfaces. These cells transport HIV from the site of infection to lymphoid tissue. The follicular DCs, found in lymphoid tissue, are also key antigen-presenting cells that trap and present antigens on their cell surfaces. In the lymph node follicles, DCs provide signals for the activation of B lymphocytes.

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Preventive Treatment After Exposure

People who have been exposed to HIV from a blood splash, needlestick, or sexual contact may reduce the chance of infection by taking antiretroviral drugs for 4 weeks. These drugs are more effective when they are started as soon as possible after the exposure. Taking two or more drugs is currently recommended.

Doctors and the person who was exposed typically decide together whether to use these preventive drugs. They base the decision on the estimated risk of infection and the possible side effects of the drugs. If they do not know whether the source is infected with HIV, they consider how likely the source is to be infected. However, even when the source of the exposure is known to be infected with HIV, the risk of infection after exposure varies, depending on the type of exposure. For example, risk from a blood splash is less than that from a needlestick.

Immediately after exposure to HIV infection, what is done depends on the type of exposure:

  • If skin is exposed, it is cleaned with soap and water.

  • Puncture wounds are cleaned with antiseptic.

  • If mucous membranes are exposed, they are flushed with large amounts of water.

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