The Human Immunodeficiency Virus (HIV) belongs to a family of viruses called the lentiviruses; it is a Retrovirus that causes acquired immunodeficiency syndrome (AIDS), a condition that causes the degeneration of the immune system. This leaves an individual more prone to opportunistic infections and some forms of cancers. HIV/AIDS is transmitted through the contact of infected Blood, semen, vaginal fluid and through breast milk; the most common way that HIV/AIDS is spread through sexual intercourse with an infected person. This paper will look at the history of HIV/AIDS, the distribution, how the HIV/AIDS infects the host and how it targets the immune system (Sharp & Hahn, 2011).
Mode of infection
A conformational change happens after gp120 binds to CD4 cells and must then bind to a second molecule at the surface of the target cells for infection to happen. Specificity of the receptor is dependent on the variant of the gp120 molecules that are expressed on its surface. Because there are several chemokine receptors that are used as co-receptors. Variations in the gp120 molecules determines which CD4 molecules can be infected by the virus, for example, HIV infection and replication through the macrophages use the CCR5 receptors and therefore it does not require high levels of CD4 molecules for infection, while infection and replication through the lymphatic system uses the receptor CXCR4 and requires high levels of CD4.
This important because it shows that the HIV can infect the host using two receptors, CCR5 is thought to be the receptor that the HIV virus uses for the initial infection since people that have a mutation in the CCR5 receptor appear to have some kind of immunity from the virus. If an individual is infected through sexual intercourse, macrophages and dendritic cells stimulate variant of malt, which provides a reservoir both locally and distally and are carried throughout the body. Exposure of the HIV infected cells to the virus promotes viral replication, a switch back to lymph tropic form of stimulation causes the further rapid distribution of the virus throughout the body. Mutation in the gp120 molecules causes the tropism of the virus in an infected person to change over time and cause the alteration of the amino acid sequence.
The virus enters the cells when the gp120 binds to the cell membrane after it binds to the CD4 and it co-receptors it allows the gp41 to penetrate the cell’s membrane and the then inject the viral particles. The cells the HIV virus targets are the CD4 cells, it infects the cells by first attaching to the cells membranes and releases its content into the cells, once in the cells the RNA is transcribed into cDNA by the enzyme reverse transcriptase. The cDNA may remain in the cytoplasm or enter the nucleus where the enzymes integrase, integrates the transcribed RNA into the host genome. Viral replication remains latent for several years while it continues to replicate at low levels.
Along mRNA strand is produced by transcribing the provirus that is spliced at the ends for the synthesis of different proteins. The first two protein made are tat and rev, tat enters the nucleus where it acts on transcription factors by binding to the LTR region this increases the rate of viral transcription. Rev also sticks to the nucleus of and to the rev the binding of rev to the responsive unit of the transcript increase RNA transport to the cytoplasm.
In the second wave of viral replication the viral core and envelope are produced and in third step un-spliced RNA is carried to the cytoplasm where it serves as a pattern for the synthesis of other viral particles. CD4 cells are released from the cells and this often leads to the cell lysing. Macrophages and dendritic cells are often not killed hence they serve as the carrier that transports the virus to other parts of the body. Dendritic cells carry the virus on the surface while macrophages allow low levels of production of HIV. Further infection and replication happen when infected macrophages and T cells are stimulated by either an antigen or cytokines.
After the virus enters the host cells and the RNA is reverse transcribed and intergraded into the DNA of the host cells. It remains latent for several years and replicates as the host cell replicates and an estimate of over 10 billion different HIV viruses are produced in an average infected person. HIV produces many different copies of the virus when it replicates because unlike normal DNA replication it does not have proofreading capabilities when there is a mutation during the replication process. The high mutation rate of HIV when it replicates is the main reason why it is doing hard to find treatments and its ability to change its surface antigens means that the immune system cannot recognise it fast.
The initial infection is characterised by flu-like symptoms, during this time the virus is in peripheral blood, this is followed by a significant drop in the number of circulating CD4T cells. The immune system responds by generating cytotoxic T lymphocytes (CLTs) and antibodies specific to the virus, these CLTs are also responsible for the drop in the number of CD4 T cells.
This is a stage in the infection that an individual presents the antibodies that are specific to HIV proteins, what follows is the partial recovery in of the CD4 cells. The distribution of the virus to the lymphoid tissue and to the rest of the body is done by the Macrophages and dendritic cells.
The high mutation of the virus makes it hard for the immune system to get rid of the virus even though the immune response is standard, for example, the latent phase of the virus can last for as long as 15 years. While the virus replicates, there is a slow decline in the number of CD4 cells.
The main location for infection is the lymph node that is why the number of virus-infected T cells in the peripheral blood remains constant. The presentation of the virus at the surface of the cells is done by the follicular dendritic cells which also act as a reservoir for the virus. Follicular Hyperplasia and lymphadenopathy happen due to continues presentation of the virus to the B and T cells, which eventually leads to degradation of the lymph nodes.
A number of factors contribute to the death of the T cells, the first one is the production of the virus in the cells, and the second one that the cells that are infected seem to be prone to programmed cell death, the third one is that CTLs kill some of the infected cells and finally CD4 T cells that are not infected are killed by bystander ADCC like mechanisms which are brought about by the binding of soluble gp120and anti gp120 to the surface of CD4 cells. During latent phase, the number of CD8 cells is more than the number of CD4 cells and AIDS starts when the levels of the CD4 t cells become low (HIV Replication Cycle,2019)
Crisis phase (AIDS)
Aids is usually diagnosed through the count of CD4 T cells, below 14% usually indicates that a person has AIDS which is characterised by the development of unusual cancer, optimistic infection and the general wasting syndrome which represents that the Virus has spread to the central nervous system.
The slow drop in the CD4 T cells count leaves an individual; prone to infection and activation of virally infected B and T cells further exacerbates immune deficiencies through the stimulation of viral transduction progeny and mutation in the CD8 cells that kill virally infected cells makes it hard for the immune system to detect the virus.
There are two forms of the HIV virus, HIV1 and HIV2, HIV1 is more virulent than HIV 2 this explains why HIV2 is mainly restricted to North Africa. The map above highlights the distribution of the HIV/AIDS.
There are two main theories that explain the origin of HIV/AIDs. The first one is the bushmeat practice theory of the people in Africa. Based on the information that HIV is directly related to the simian immunodeficiency virus (SIV) that is found in chimpanzees’ scientists have theorised that SIV may have mutated to HIV in Africa through continuous exposure of SIV.
The initial description of HIV/AIDS was in 1981 when unusual cases of pneumonia were reported among previously healthy homosexual males in America. This was followed by the recognition of an aggressive form of Kaposi’s sarcoma, since the first reported case thereof HIV/AIDS in 1981 there are now over 30 million people infected worldwide.
When AIDS was first discovered it seemed to be restricted to gay men, drug user and Haitians that lived in the United States and if AIDS was confined to these high-risk population the rest of America felt safe. This however changed when a child contracted AIDS after she was blood transfused. Later that year there were reported cases among bisexual men and women, after these cases no one was denying that AIDS was spreading to the rest of the population.
In 1982 scientists in France led by Lu Montaginer and Froncoise Barre- sinoussi isolated a new virus from an AIDS sufferer. Later in 1984 workers at the cancer institute in America also announced that they had managed to isolate the virus that causes AIDS they called it (HTLVIII) which means the human T cells virus which was later named as human immunodeficiency virus. The causes of AIDS were not identified until three years later, and soon after that the genome was sequenced, and the clinical tests were developed (Sharp & Hahn, 2011).
The list below highlights the HIV/AIDS timeline
- 1981 – 108 cases of AIDS reported in the US
- June – five gay men in los angles
- July – eight gay men reported with severe immunodeficiency
- December – cases of AIDS in intravenous drug users
- December – the first AIDs case reported in United Kingdom
- By 1982 around 593 cases of AIDS were reported and with the morbidity of 243
- June – a cluster of AIDS cases in California suggest an infectious agent
- 1982 – Acquired immunodeficiency was given as the new name
- December – a 20 months year old baby dies of AIDS due to multiple transfusions
- By 1983 the mortality had gone up to 759 people
- 1094 the mortality had gone up to 6,993
- November CD4 molecules on the T cells identified as the receptor for the virus
- by 1986 the mortality had gone up to about 16000, and in May of the same year the name human immunodeficiency virus was given to the virus that causes AIDS
HIV can be divided in two the HIV1 and HIV1; they can be described as an enveloped retrovirus that belongs to a family of virus called the lentivirus. The viral particle contains two strains of identical RNA and three enzymes called integrase, protease and reverse transcriptase.
These are packaged into p24 core antigen with a p7 nucleoprotein and p9. All these are surrounded by a p17 matrix protein. Antigens presenting cells like dendritic cells, macrophages as well as the CD4+T cells are potential targets for the virus because they display CD4 makers on their surface. This is because the viral envelop that is derived from the host cell display viral glycoprotein gp120 and gp41, the gp120 which is covalently bonded to gp41 is very important for infection.
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