How the HIV Virus overwhelms the Immune System

 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 were 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 also its ability to change its surface antigens means that the immune system cannot recognise it fast.

Initial infection

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.

Latent phase

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.

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.



Differences in infection and malignancies reflect the patterns and mode of infection in individuals with AIDS, in some cases individuals infected with HIV may also be infected with another sexually transmitted virus. This may lead to the development of some aggressive form of cancers which are thought to be caused by oncogenic viruses and further immunosuppressive start.

For example, human papillomavirus which is associated with the development of cervical cancer and some aggressive forms of Kaposi sarcoma is virally unique to AIDS patients’ in particular male homosexuals. Kaposi sarcoma is caused by the human herpes virus 8 (HHP-8), this is associated with unusual forms of lymphomas and primary effusion lymphoma which are worse in homosexual males. Also, central nervous system cancers are common in AIDS patients. Other cancers include squamous cell carcinoma of the head and neck and atypical Hodgkin lymphoma.

The development of infectious diseases in AIDS patients is due to the lowered activity of the cell-mediated immune system.   This makes a person more prone to opportunistic that is caused by ordinarily non-pathogenic bacteria that are either found in the body as part of the healthy flora or on the surface of the skin. Some examples of T cells immunodeficiency are PCP complication and candidiasis.

Granuloma formation which is T cell dependant is also weak in AIDS patients this leads to uncontrollable mycobacterial infections, for example, Mycobacterium avium which is usually not human pathogens can cause overwhelming infections also diarrhoea in the gastrointestinal tract is mainly caused by the microorganisms’ cryptosporidium, mycobacteria avium and CMV.

Necrosis in AIDS is caused by continues infections, which results in constant stimulation of the immune system by the microorganism and the dead cells debris.  The B cells show evidence of responding to the stimulation, the complication of this is the rise in the levels of serum immunoglobulin, rise in circulating immune complexes and an increase in plasma cell production. Patients are still not able to mount an immune response to newly encountered toxins even though there is marked an increase in the number of circulating B cells.

AIDs-related dementia and inflammation of the brain are probably due to the infection that is carried by the macrophages which infect cells of the brain like microglia, oligodendrocytes, and astrocytes this is seen in 50% of AIDS patients.  The last stage of AIDS is a condition called Cachexia which means general wasting, how is occurs is largely unknown.

One suggested theory is the alteration of cytokine action of macrophages by the HIV virus to increase production of TFN which leads to extreme weight loss. The recognition of the virus is dependent on the molecules that recognise antigens found on the major histone complex on chromosome 6. This area of the gene can change very fast. The inheritance of the HLA is significant to the outcome of the infection, this why some individuals tend to have partial immunity to the virus.


The most common way most of the viruses are detected is through antibody testing, as with any infection when infected the body produces antibodies to that particular infection. In the case of the HIV virus when an individual is infected, they produce antibodies which can be detected using a diagnostic procedure called the enzyme-linked immunosorbent assay (ELISA).

If an individual is positive for the virus, the colour on the ELISA will change when the antibodies bind to the antigen on the surface of the well, in some cases where an individual gets a positive result or negative they are told to have another blood test in six months. This is because the ELISA is very sensitive and can sometimes show a false positive or negative.



Richard coico, G. s. (2009). immunology a short course john Wiley & sons

S, J. (2007). Diagnosis of HIV-1 Infection in Children Younger Than 18 Months in the United States. Journal of American academy of paediatrics. from



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