The Human Immunodeficiancy Virus
(HIV) has been documented as the worst pandemic in human history. Yet despite
approximately 70 million contracted cases, accounting for more than 35 million
deaths, a definitive cure has evaded researchers to this date for a number of
reasons. For one, rapid antigenic drift means that the intricate acquired
immune system of humans cannot keep up with the constantly changing antigenic
make-up of the HIV's surface (surface coat of the virus frequently changes). The HIV retrovirus also has a target immunocyte,
the CD4+ helper t cell. By attacking the cells that signal, synthesise and
mediate the function of the CD8+ cytotoxic t cells amongst other immune
effectors, they further reduce the chances of the immune system defending
against the infection. HIV is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), a condition in which failure of the immune system enables opportunistic infections and cancers to thrive. HIV is a blood-borne virus that can be transmitted via the transfer of blood, semen, vaginal fluid or breast milk.
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| An HIV viral molecule. |
Acquired Immune Response
One
of the main systems which sets out higher vertebrates from their invertebrate
counterparts, is a sophisticated, well-developed immune system. The acquired,
or adaptive, immune system, enables humans to recognise non-self pathogens as
well as creating an immunological “memory” whereby repeated infections by the
same strain of a disease will be recognised and defended against more
efficiently. The cells responsible for this task are the T and B lymphocytes.
The CD4+ Helper T cell are vital to proper immune function. These
cells aid B cells in producing antibodies, recruits neutrophils, eosinophils
and basophils to infection site, inflammation and through cytokine and
chemokine signalling, orchestrate the many components of immune response. Another prominent immune effector
in mammals are the CD8+ Cytotoxic T cells. These immunocytes recognises and
binds to specific viral antigens on infected cell surfaces and releases
chemicals to destroy the cell before the virus can enter the nucleus and begin
replication. The HIV
virus is so devastating to the human body as it selectively invades the CD4+
Helper t cells; the HIV envelope glycoprotein gp120 binds to to the surface of
the CD4+ helper t cell followed by internalisation. This renders them incapacitated and prevents
them from mediating the intricate immune response. Furthermore, the HIV virus
targets macrophages which are major effectors in phagocytosing, engulfing and
digesting pathogens and cellular debris. HIV infects these cell types in different ways however as CD4+
cells are generally eliminated by host pathogenic effects whereas macrophages
physically survive, acting as an infection containing reservoir.
Why HIV is able to successfully hide from the immune system
Antigenic variation is a
prominent factor in a diseases resistance to a host immune system. HIV is a retrovirus meaning that the enveloped virus replicates within the host cell via reverse transcription. Once the single stranded RNA enters the host cell cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA. Now, normal transcription is subject to massive amounts of proof reading to prevent any sort of mistakes and therefore mutations. HIV reverse transcription harbours no mechanisms of proof reading and therefore every viral replication produces mutated versions. As it replicates so quickly, millions of varying strands of the virus are produced within a single host so that even when the acquired immune system recognises a particular strain, many more are already going undetected. This mechanism of producing many mutated strains is an effective method of immune avoidance but it is not under the control of the virus itself. Often, less effective or benign strains of the virus are produced but due to the sheer magnitude of viral replication, enough harmful strains are produced to be effective.
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| An HIV virus binding to the CCR5 receptor of a CD4+ helper T cell and entering the cytoplasm. |
Treatment of HIV
Historically, the stigma of HIV has been that it is a death sentence, however advances in medicine have dramatically increased not only the standard of living of patients, but also their longevity. Highly Active Antiretroviral Therapy (HAART) maintains immune system function as well as preventing opportunistic infections normally associated with a depleted immune system. Treatments have also meant that HIV progression into AIDS is becoming increasingly rare. A paper published in 2012 has suggested that as many as 700,000 lives were saved in 2010 as a direct result of antiretroviral therapy. Prior to treatment, the average life expectancy of someone infected with HIV was 9-12 years post-infection. Now, patients can live to their normal life expectancy despite carrying the disease, however as a cure is still not available, they can still transmit the infection.
Future of Cure and Vaccine Research
As it stands, there is no way of curing or preventing HIV. Obviously, there is ongoing research into more efficient and effective retroviral treatment but the main priority should be into a cure the virus, or even better a vaccine to prevent it in the first place. Efforts have been placed on targeting the gp120 on the surface of the virus that binds to the CCR5 receptor on the CD4+helper T cell. There are documented cases of individuals who possess a 32 base pair deletion on their CCR5 receptor that are technically immune to HIV. Studies on these particular mutations could pave the way to a definitive vaccine.
Thankfully, we live in an age where treatments are available but many of the sufferers of HIV do not have access to such therapy. The disease is most prevalent in Africa where a combination of lack of education about the disease and lack of funds to afford treatment make it particularly devastating. Awareness saves lives and there should be no stigma to being tested. Preventing the spread of the disease can be as important as developing a cure. I find this disease as fascinating as it is devastating so if you would like to know more about it, I would be happy to answer any questions.
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| Prevalence of HIV, the predominance of cases are in Africa due to lack of education and access to treatment |
