The Evolution of HIV, Mutation Causing Drug Resistance, Term Paper Example

Abstract

The HIV virus is regarded as the world’s most dangerous infectious disease, responsible for 1.5 million deaths globally as of 2013. With the growing numbers of new infections and the concern of the development of drug resistant strains, there is an inherent need to understand the causes of drug resistance. This paper looks at the different strains of the virus and what generally causes the development of drug resistance in all strains.

Origins

The origin of the HIV virus is generally accepted to be wild apes found in West African forests. It is believed that the HIV virus mutated from a similar virus, the Simian Immunodeficiency Virus (SIV), which is present in West African ape populations. The while the mutation relied on a number of factors and variables, a cross-species transfer is believed to have introduced the virus to human populations within the West African region.

The First Exposure

While it had been generally believed that the spread of the SIV virus in human populations in the late 19^th and early 20^th century was responsible for the initial exposure to the SIV virus, this theory does not hold. Cross-species interaction between the apes and human populations of West Africa have existed before the colonial era. Numerous factors, mainly the social changes that took place at the time led to the first exposure.

The cross-species transfer of SIV from apes to humans was particularly high at the time when West Africa was under colonial rule. This was because the burgeoning colonial cities were constantly supplied with cheap bush meat to sustain the slave populations. This increased contact led to transfer of the SIV virus with individuals who hunted, treated or were cut in the process of hunting and treating the bush meat. Blood interaction between the apes and human being led to the rapid cross-species transfer of the virus. However, this was not sufficient for the mutation of SIV to HIV.

As colonial enterprises grew and living conditions for the colonized West African population deteriorated, the ideal conditions for the first exposure were being laid. The poor working conditions and the growth of urban colonial cities led to the significant social changes. Slavery and the forced labor camps encouraged the thriving of prostitution, a factor that led to the increase in genital ulcer diseases (GUD), which are genital ulcer causing diseases (Sharp and Hahn). These diseases are usually transmitted via sexual intercourse and they include genital herpes and syphilis.

Marx, Alcables and Drucke, held the notion that serial passage was responsible for the SIV virus to adapt to the human host to mutate into the HIV virus. They postulate that serial transmission or passage is critical for the eventual mutation of the virus. This is based on the theory that a virus increases its adaptation in a new host species through rapid transmission between hosts within the same species. If this process occurs when the hosts are still in the acute infection stage, an adapted variant of the virus emerges as a result of progressive adaptive mutations. As such, the most important factor that led to the first case of HIV exposure was a result of the increase in GUD cases in colonial West Africa.

HIV Strains

The HIV virus is one of the most variable viruses known to man owing to its ability to readily mutate. To date, there are two type of HIV that exist, i.e. HIV-1 and HIV-2 and a host body can be found to have numerous strains of both HIV-1 and/or HIV-2. Both species of HIV originate or have mutated from an SIV that is found in apes and are mainly transmitted through blood, sexual contact and mother-to-child transmission (Wertheim and Worobey).

HIV-1

This species of HIV originates from an SIV that is found in chimpanzees, also known as SIVcpz. However, other strains of this species of HIV have been found to originate from an SIV that affects the Gorilla gorilla gorilla (the western lowland gorilla), known as SIVgor. This type of HIV is the most easily transmitted through bodily fluids and is makes up the majority

As depicted in the figure, the HIV-1 type virus has four distinct groups, M, N, O and P. each group represents a unique and distinctive introduction of an SIV into the human species. Group M (Main/Major) constitutes the majority of the HIV-1 infections and is most common globally. Over 90% of HIV-1 infection are attributed to the Group M HIV strain. This group has nine clades, or genetically distinct subtypes. However, other subsets of the groups are formed as a result of “viral sex”, i.e. the sexual reproduction, between two distinct subtypes. These strains are referred to as CRFs (circulating recombinant forms) which usually die off after a while. The mixture between clade A and D would be referred to as CRF A/D. The following are specific facts about each subtype.

• subtype A is predominantly found in West and Central Africa
• Subtype B is most common in men who have sex with other men in the Australia, Japan, Europe and the Americas
• Subtype C is the most chief subtype, accounting for around 50% of global infections. Predominantly found in Nepal, India, Southern and East Africa.
• Subtype D is generally geo-restricted to East and Central Africa
• Subtype F is found is dispersed in Eastern Europe, Central Africa and South America
• Subtype H is geo-restricted to Central Africa
• Subtype J is geo-restricted to Central America
• Subtype K is geo-restricted to Cameroon and the Democratic Republic of Congo
• CRF A/E originated in Central Africa but is currently mainly found in South East Asia.
• CRF A/G is commonly found in Central Europe, West and East Africa(Sharp and Hahn)

Group N is more specifically geo-restricted to Cameroon. This strain is exceptionally rare and was first discovered in 1998. Group O (outlier), i.e. the outlier group is geo-restricted to West African regions and is rarely detected outside these locations.

HIV-2

This species of HIV originates from an SIV that is found in the Cerecocebus atys atys (sooty mngabey) a monkey that is native to the regions of West Africa. This type of the virus is less easily transmitted than the HIV-1 type (Wertheim and Worobey). This is because it has a longer period in the middle of initial infection and actualization of illness symptoms. This type of the virus is rare and is restricted to Ivory Coast, Sierra Leone and Liberia. There are eight groups of HIV-2, A through H. Group A and B are known as the epidemic groups, with each of the remaining of the groups having been identified in single sets of two people per group.

Genome and Drug Resistance

The HIV virus has since the 1980s significantly evolved, leading to the occurrence of a new challenge, the development of drug resistant strains of the HIV virus. ART (antiretroviral therapy) has significantly assisted in reducing the morbidity and mortality rate as a result of HIV (Pennings). However, the way in which ARTs work on eliminating or diminishing the population of the virus leaves room for the development of a stronger and drug resistant strain. The development of drug resistant HIV strains is currently a global issue that raises concern within the health and medical fields.

As a result of antiretroviral drug therapy procedures the HIV virus has been able to experience an accelerated microevolution. This is because the nature and biological behavior of the HIV virus leads to the virus developing resistance to these techniques in the long-term. There is considerable possibility that human intervention in treating the virus continues to enhance the microevolution of the drug towards a completely resistant virus.

Cause of Drugs Resistance

The HIV virus works in a unique way, unique from any virus that is known to man. Owing to the fact that HIV is a retrovirus, it reproduces its RNA genome as a result of the synthesis process that occurs between the DNA contained within the genome and the reverse transcriptase found in the host (Johnson, Brun-Vézinet and Clotet). This is because this process creates the ample environment for the process of natural selection to take place, remedying the effects of the errors that result in the DNA synthesis process.

The process of natural selection leads to the development of mutations that can accrue within a given HIV population over years, decades or even centuries, leading to a great variation in the virus over time within a given population. As this genetic variation in the population increases, the possibility of a particular strain gaining an evolutionary selective advantage. As the HIV population continues to subject these strains to drugs (ART), natural selection leaves only the strains that capable of adapting to the effects of the drugs on its cellular structure. These surviving strains can then combine to form a new strain or population that is immune to the effects of the drugs.

Since patients will have taken drugs, they will initially experience success with the treatment. This is during the process of natural selection when the virus population within the host is significantly reduced. However, at some point, success with treatment will begin to decline. This decline will continue to the point where the virus will be completely resistant to the drug. It is during this process that the virus load within the patient increases, the immune virus strain populations surge as it rapidly multiplies the RNA genome against the diminishing effects of treatment on the virus.

Drugs and Other Treatments

HIV is mainly treated using 6 types of drugs that are classifies as antiretroviral. This classification is due to their actin on the retrovirus HIV. The drugs are further categorized according to their action on the different stages of the replication of the HIV virus.

1. Entry Inhibitors

As the name suggests, these inhibitors impede the ability of the virus to gain entry to the human body. Because the virus gains entry through binding itself to the receptors found on the exterior surface of the cell. Cell infection is averted when the process of binding to the receptor is unsuccessful.

2. Fusion Inhibitors

These inhibitors impede the virus’ entry into the body by negating the ability of the HIV virus to fuse with any given cellular membrane.

3. Reverse Transcriptase Inhibitors (RTIs)

The HIV virus has to convert its single-strand RNAs into HIV DNA, which is double-stranded. In order to accomplish this, the virus uses enzyme reverse transcriptase (RT). These inhibitors prevent the action of enzyme reverse transcriptase. Two kinds of RTIs are used in ART.

NRTIs (Nucleotide/Nucleoside RT Inhibitors) stop the synthesis of HIV DNA by introducing faulty DNA building blocks to developing HIV DNA chains.

NNRTIs (Non-nucleoside RT inhibitors) stop the development of HIV DNA from HIV RNA by binding to enzyme reverse transcriptase. (Wain, Bailes and Bibollet-Ruche)

4. Integrase Inhibitors

When the virus gains entry into the cell membrane, it uses an enzyme, enzyme integrase to integrate its own genetic material into the infected cell’s DNA. These inhibitors block enzyme integrase.

5. Protease Inhibitors

The HIV virus requires an enzyme, enzyme protease, to slice the long HIV proteins into smaller ones. These inhibitors impede the work of protease to avoid new virus particle association.

6. Multi-class Combination Products

These are a combination of HIV drugs from different classes. These have numerous simultaneous actions on different stages of the multiplication of the HIV virus. (Pennings)

In conclusion, while the HIV virus is currently renowned as the world’s highest killing infectious disease, efforts to curb the disease have since proven futile in the long-run. Owing to the nature of the virus, it biological functionality and processes, it gradually gains resistance against popularly used antiretroviral treatment. The two main HIV groups, HIV-1 and HIV-2 continue to develop immunity against treatments through the process of natural selection. This raises question as to the efficiency of human intervention in treating HIV/AIDS. There is considerable need for the development of more effective and long-lasting solutions that require scientific innovation.

Works Cited

Johnson, Victoria A, et al. “Update of the drug resistance mutations in HIV-1: December 2009.” Top HIV Med 17.5 (2009): 138-145. Internet Source. 19 June 2015. <https://www.iasusa.org/sites/default/files/tam/18-5-156.pdf>.

Pennings, Pleuni S. “Standing Genetic Variation and the Evolution of Drug Resistance in HIV.” PLOS Computational Biology 8.6 (2012). Internet Source. 19 July 2015. <http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002527>.

Sharp, Paul M and Beatrice H Hahn. “Origins of HIV and the AIDS Pandemic.” Cold Spring Harbor Perspectives in Medicine 1.1 (2011). Internet Source. 19 July 2015. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234451/>.

Wain, Louise V, et al. “Adaptation of HIV-1 to Its Human Host.” Molecular Biology and Evolution 24.8 (2007): 1853-1860. Internet Source. 19 July 2015. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053193/>.

Wertheim, Joel O and Michael Worobey. “Dating the Age of the SIV Lineages That Gave Rise to HIV-1 and HIV-2.” PLOS Computational Biology (2009). Internet Source. 19 July 2015. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669881/>.

Wheeler, William H, et al. “Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, US–2006.” Aids 24.8 (2010): 1203-1212. Internet Source. 19 July 2015. <http://journals.lww.com/aidsonline/Abstract/2010/05150/Prevalence_of_transmitted_drug_resistance.15.aspx>.