Dcartmel Week 3

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Drew J. Cartmel

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Scientific Purpose

The purpose of this assignment is to further understand the reasons that explain why the HIV-1 virus is able to adapt to its host environment through its tendencies to diversify and diverge from its original evolutionary forms.

Definitions

Seroconversion- the stage in an immune response when antibodies to the infecting agent are first detected in the bloodstream (Dictionary of Biology Oxford Reference eBook, 2008).
T Cell- A type of lymphocyte manufactured in the thalamus gland that is involved in the cell-mediated response (Oxford Dictionary of Zoology eBook, 2009).
Chemostats- an apparatus allowing for the continuous cultivation of bacterial populations in a constant, competitive environment in which bacteria compete for a limiting nutrient in the medium (Oxford Dictionary of Genetics eBook, 2007).
Cohort- a group of individuals of the same age (Dictionary of Ecology Oxford Reference eBook, 2010).
synonymous mutation- do not change the amino acid sequence of the gene product and therefore can be silent mutations that have no effect on the function of the encoded protein (A Dictionary of Genetics, 2014).
Monophyletic- In systematics, describing a group of organisms that contains all the descendants of a particular single common ancestor (Dictionary of Biology Oxford Reference eBook, 2008).
Nested- placed or stored one inside the other (Dictionary of Biology Oxford Reference eBook, 2008).
Epitope-The structure on the surface of an antigen that is recognized by and can bind to a specific antibody (Dictionary of Biology Oxford Reference eBook, 2008).
Coreceptors- A receptor molecule on the surface of a cell that enhances the activity of another receptor following binding of its extracellular ligand (Dictionary of Biology Oxford Reference eBook, 2008.)
Immunological- Of, concerned with, or pertaining to immunity or immunology. (Oxford Dictionary of Biochemistry and Molecular Biology eBook, 2008).

Outline of Paper

What is the importance or significance of this work?

The significance of this work is that it can provide researchers information regarding the capabilities of the HIV-1 virus to adapt to selection forces that are imposed upon it by its host organism and how such forces drive the overall evolution of the virus.

What were the limitations in previous studies that led them to perform this work?

The limitations in previous studies that led the authors to perform this work were that such studies focused on very small groups of people, did not directly investigate sequence patterns, and didn't collect sufficient amounts of time points for test subjects.

How did they overcome these limitations?

The authors of this paper overcame these limitations by following 15 participants that were assessed at 6 month intervals for up to four years.

What is the main result presented in this paper?

The main result presented in this paper was that with regards to HIV-1 variants, higher levels of genetic diversity and divergence corresponded to larger CD4 T cell decline in individuals screened.
It was also found that there was possible selection against changes in amino acids in viral strains from non-progressors while progressors exhibited such selection for amino acid change.

What are the methods used in this study?

This study followed 15 participants who were injection drug users.
Blood samples were obtained from the participants at 6-month intervals for up to 4 years.
Researchers utilized a nested PCR method to amplify a specific 285 base pair region of the env gene found in peripheral blood mononuclear cells.
A Reverse transcription-PCR method was used to determine the plasma viral load.
Phylogenetic trees were then created by using the MEGA computer package.
Correlations were then made between the genetic diversity and CD4 T Cell count one year after the study began.
Differences between strains were categorized as synonymous or nonsynonymous based on comparison between initial consensus sequences and subsequently observed strains.
Subjects 9 and 15 were analyzed further due to high observed genetic variation after the first visit in order to determine if they were infected with different viruses altogether.
Slopes from regression lines over time were then created for each of the three progression groups and were then compared with random effects models.

Briefly state the result shown in each of the figures and tables

Figure 1:This figure shows the cell counts, diversity, and divergence of CD4 T Cell counts of all of the 15 subjects over the four year study period. The patterns of CD4 T Cell decline were different between all of the participants studied.
Table 1:This table shows a summary of the data collected on the fifteen participants in the study. Various results were found from the data in this table such as the fact that there was a large range of both increases and decreases in the CD4 T Cell counts between the individuals. It was also concluded from this table that thirteen of the fifteen participants showed viruses that were very homogenous in their initial visits.
Figure 2:These graphs demonstrated the mean slope per year of intravisit diversity and divergence in the three progressor groups. It was found that there was an increase in diversity and divergence in all three groups over time. It was noticed that the increases in diversity and divergence were greater when moving from nonprogressor to rapid progressor groups.
Figure 3:This figure shows the phylogentic tree created for subject 9. This tree demonstrates the finding that there was no evidence of predominance of a single strain throughout the study.
Figure 4:The figure shows the phylogenetic trees of four randomly selected participants from the original group. This figure demonstrates the finding that there were some individuals who showed a pattern of limited progression along a single branch in their phylogenetic trees as well as a return to strains resembling those seen at previous visits.

How do the results of this study compare to the results of previous studies?

With regards to the previous study carried out by McDonald et al, they they found similar results in terms of greater genetic divergence being observed in three of the five rapid progressors that were analyzed. This current study found differences in diversity observations compared to this specific previous study which was most likely due to differences in amount of samples taken from the individuals as well as the time in which the participants were followed.
With regards to the Wolinsky et al study, there were similar results found in terms of rapid progressors that showed comparable diversity and divergence patterns, however this previous study was not able to determine any effective immune responses to the viruses in rapidly progressing patients.
Similar results in terms of CD4 T Cell decline as well as increased genetic diversity and divergence were found in the model produced by a previous study carried out by Nowak.

How do the results of this study support published HIV evolution models?

The results of this study support the published HIV evolution models because they show that there was an increase in genetic diversity and the appearance of strains that resembled those that were previously dominant in the hosts. It also showed that the host immune response targeted the most frequent virus present rather than targeting a broad range of viruses.

What are the important implications of this work?

The important implications of this work are that the HIV virus is a very dynamic virus in that it has the ability to adapt to changing environments. This paper's focus on CD4 T Cells provided a solid example of how this virus can evolve to survive in harsh environments and why it has the ability to produce a deadly disorder.

What future directions should the authors take?

A possible future direction that the authors could take is to see whether there are viruses other than the HIV virus that exhibit comparable evolutionary/adaptability capabilities in response to the human immune system.

Give a critical evaluation of how well you think the authors supported their conclusions with the data they showed. Are there any limitations or major flaws to the paper?

I think that the authors of this paper did support their conclusions thoroughly with the data that they presented. These authors built on the previous work of other studies with methods that were more specific and that addressed problems such as follow up times that were not long enough and not enough data taken from each of the participants during the study as a whole. I think that their use of phylogenetic trees was a very good method of explaining the reasons behind why they observed the results that they found. Overall, I think that the data that was presented in this paper did support their findings regarding the genetic diversity and divergence shown by the viruses in response to the host immune systems.

Scientific Conclusion

The main result of this paper showed how the HIV-1 virus is able to adapt and evolve to its host environment. This virus has the capability of diversifying and diverging from it original form in order to allow for survival in harsh host environments where it is opposed by immune systems. This study was important because it added to the knowledge of how this virus evolves and using these findings, other researchers can possibly make further progress in the development of methods to combat such a virus in the future.

Acknowledgements

My partners this week were Nathan On and Carolyn C. Egekeze. We did not collaborate on this assignment in class or outside of class.

I copied and modified the protocol shown on the Week 3 page.

Except for what is noted above, this individual journal entry was completed by me and not copied from another source.

Dcartmel (talk) 23:09, 5 February 2020 (PST)

References

OpenWetWare. (2020). BIOL368/S20:Week 3. Retrieved February 5, 2020 from https://openwetware.org/wiki/BIOL368/S20:Week_3

Elizabeth Martin and Robert Hine, (ed.). (2008). A Dictionary of Biology (6th ed.). Retrieved February 5, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803100456149.

Michael Allaby. (ed.). (2009). A Dictionary of Zoology (3rd ed.). Retrieved February 5, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803102746823.

Robert C. King, William D. Stansfield, and Pamela K. Mulligan, (ed.). (2007). A Dictionary of Genetics (7th ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803095605506.

Michael Allaby. (ed.). (2010). A Dictionary of Ecology (4th ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803095622565.

Robert C. King, Pamela K. Mulligan, and William D. Stansfield. (ed.). (2014). A Dictionary of Genetics (8th ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/view/10.1093/acref/9780199766444.001.0001/acref-9780199766444-e-6654?rskey=0NkIjz&result=2.

Elizabeth Martin and Robert Hine, (ed.). (2008). A Dictionary of Biology (6th ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803100206349.

Elizabeth Martin and Robert Hine, (ed.). (2008). A Dictionary of Biology (6th ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/search?q=nested&searchBtn=Search&isQuickSearch=true

Elizabeth Martin and Robert Hine, (ed.). (2008). A Dictionary of Biology (6th ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803095755256.

Elizabeth Martin and Robert Hine, (ed.). (2008). A Dictionary of Biology (6th ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803095638966.

Richard Cammack, Teresa Atwood, Peter Campbell, Howard Parish, Anthony Smith, Frank Vella, and John Stirling, (ed.). (2008). Oxford Dictoinary of Biochemistry and Molecular Biology (2nd ed.). Retrieved February 6, 2020 from https://www.oxfordreference.com/view/10.1093/oi/authority.20110803095958845.

Markham, R. B., Wang, W. C., Weisstein, A. E., Wang, Z., Munoz, A., Templeton, A., ... & Yu, X. F. (1998). Patterns of HIV-1 evolution in individuals with differing rates of CD4 T cell decline. Proceedings of the National Academy of Sciences, 95(21), 12568-12573. doi: 10.1073/pnas.95.21.1256.