The Gene to Cure HIV: APOBEC3G (aka CEM15)
"This web page was produced as an assignment for an undergraduate course at Davidson College."
General Information(NCBI 2006, UniProt 2006, Sheehy et al. 2002)
The Gene Discovery
Scientific Literature vs Popular Sources
Categories covered by the Articles:
In 2002 an article was published in Nature by Sheehy, et al. called The isolation of a human gene that inhibits HIV-1 (human immunodeficiency virus 1) infection and is suppressed by the viral Vif protein. This paper introduced the discovery of the gene CEM15 and its potential in fighting HIV-1. The content and presentation of this article can be broken up into five main categories: why they started looking, how they identified the possible gene, how they tested the gene to support their identification, how they characterized the gene, and what possible mechanisms are run by the gene in order to suppress HIV-1.
The 2002 Times, London article "Scientists find gene that fights deadly HIV: Discovery provides new target for AIDS treatments" covers the discovery of the gene in contexts both similar to and different than the scientific publication: what was discovered, why this seems especially relevant, how they found the gene's function, and the basic workings of the virus it fights.
Categories that seem both similar and different:
The basic premise is the same in both the scientific and popular press articles: the gene CEM15 has been identified as the gene that conveys antiviral resistance when it is not being suppressed by vif.
The split comes quickly after the basic premise. The scientific article desires to show how the authors discovered that CEM15 was the most likely candidate. They explain how they used northern blot analysis and present the results for our verification. Meanwhile, the popular press gives only a brief nod to the fact that prior research pointed to a natural defense against HIV in the cell before immediately going to CEM15 being an integral part to the system. They do not acknowledge that other possibilities were investigated but test results indicated CEM15 is the gene that causes the resistance.
The methodology employed to verify function provides essential support to discoveries such as this (Kua et al. 2004). In this case the popular press does acknowledge the necessity of some mention of how CEM15's function was verified.
While the Times does mention how the researchers came to accept their theory, the process is highly simplified and condensed to one line. One job of a popular press article is to translate the science into something understandable to a general audience. Some people might think that further explanation or inclusion of methods would confuse the audience, but I think that a mention of the control where there was no vif and no CEM15 could have enhanced the audiences knowledge and acceptance by presenting the sharp contrast in viral production (see figure from Nature below, permission pending). Sheehy et al. goes in depth about all of the methods and controls used to support their theory. While all of this information is helpful to peers that are checking the accuracy and credibility of the findings, the information would have served to confuse a more general audience. If the popular press had attempted to put in the full methodology and results, clarity and understanding would have been lost to the readers.
While one might think that the scientific paper's explanation of why they started looking for this gene might have a direct correlation with the popular press's explanation of why this find is particularly relevant, the connection seems lacking.
Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein focuses on how prior experiments provided insight into the existence of an antiviral system. Without the previous research, Sheehy, Gaddis, Choi, and Malim would not have had any reason to suspect that CEM15 coded antiviral proteins. While the hope of finding new drugs and treatments to fight HIV-1 is the basic drive for this type of research, this publication focuses on what new information spawned the search. The implications of the find for new treatments comprise only the last few sentences of the last paragraph.
The relevance discussed in "Scientists find gene that fights deadly HIV: Discovery provides new target for AIDS treatments" pertains not to earlier experiments but to the information presented during the International AIDS conference about the necessity of new kinds of drugs. At least two thirds of the article talks about the therapeutic potential of the discovery in relation to the expressed need for new approaches to HIV treatment. Whereas the scientific paper accounted for therapeutic potential only briefly at the end, the popular press focused on the therapeutic potential while giving only cursory mention to previous studies that laid the grown work for searching for this gene (Sheehy et al. 2002, Henderson 2002).
The shifted focus in the popular press makes sense because audiences often care more about the potential applications of science then the historical scientific context. The single sentence mention of the previous experiments at least provides some context for how they even knew that something like CEM15 existed.
Missing Links (Categories that do not cross):
The public access genomic databases provide useful tools for better understanding a new gene. The scientific paper takes the time to review the searches because the comparison of genes can give insight to function. The searches for CEM15 and its generated protein sequence revealed that their is a closely related gene expressed in cells in MDS patients and, that while there is a murine ortholog of the protein, there is no ortholog in the commonly studied organisms of yeast, fruit flies, or C. elegans. The real success with the database search came from the alignment of CEM15 with apobec-1 and phorbolin-1. The alignment showed similarity in the zinc-binding domain that is essential for catalytic activities of mammalian apolipoprotein B mRNA editing enzyme (of which apobec-1 is a subunit) and phorbolin. This information suggested to the researchers that CEM15 could be operating a similar function to neutralize HIV-1 when it is not suppressed (Sheehy et al. 2002).
While the popular press could not have gone into the details of the searches, it completely leaves out the characterization of the gene through comparison with previously defined genes.
The puzzle of a gene seems incomplete without some understanding of the mechanism or possible mechanisms run by the gene. Without a potential mechanism, we could not be sure that the gene in question was actually responsible and was not expressed as a result of a different gene that was actually in charge. Without some possibilities for how the protein or gene product functions, we could not blindly assume its actions to be the main cause of an observed activity. In the case of antiviral activity caused by CEM15, Sheehy, Gaddis, Choi, and Malim succeeded in providing potential mechanisms for CEM15's proposed antiviral activity. The similarity between CEM15 and mRNA editing enzymes allows them to make conjectures about where in the life cycle the inhibition of HIV takes place and how the gene succeeds in causing it.
Science journalists are supposed to be the watch dogs of the people as well as the translator (Kua et al. 2004). While going in depth into the mechanism would probably leave a general audience confused, the article should at least acknowledge the potential mechanisms that support the claim that CEM15 is the gene causing the antiviral activity. The public has some assurance by the brief mention of the methods, but an acknowledgement of some possible ways that the gene produces this effect would have created firmer support.
The Times article includes a brief summary of how HIV infects and spread by Dr. Malim. This is located at the very end of the article after mentioning that the virus somehow interferes with the genes lifecycle (Henderson 2002). This summary of HIV infection provides important information about the disease this gene fights. It almost seems that this summary could have acted as a good transition to a comment on how based on their findings the researchers propose that the gene works in the later parts of this cycle.
While the popular press rightly includes a summary of the virus's life cycle, the Sheehy et al. article did not need one and as such did not provide one. An article in a scientific paper is only given so much room. Including information on the lifecycle of HIV would have taken up space that was used to fully explain a procedure or give predictions on the gene's function. Because the audience of the article is made of scientific peers, most would have same basic understanding of retroviral lifecycles.
When the paper was first written it was unknown whether CEM15 made up only part or all of this antiviral system. The possibility that other genes could be contributing to the antiviral activity is acknowledged, but did not have enough support to say if any genes really were or what they are (Sheehy et al. 2002).
Henderson M. 2002 July. 15. Scientists find gene that fights deadly HIV: Discovery provides new target for AIDS treatments. The Times, London. In: LexisNexis Academic [database on the internet]. LexisNexis; c 2006-[cited 2006 Sept. 10].[about 1 page].Available from < http://web.lexis-nexis.com/universe/form/academic/s_guidednews.html?_m=bd1627c744ee2b82a92dbcaec10c437b&wchp=dGLbVzz-zSkVA&_md5=9a07a3918804ee2fde29feaebcb876b3 >.
Kua E, Reder M, Grossel MJ. 2004. Science in the news: a study of reporting genomics. Public Understanding of Science. 13:309-322.
NCBI. 2006 Sept. 6. APOBEC3G apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3G [Homo sapiens].<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=60489>. Accessed 2006 Sept. 10.
Sheehy AM, Gaddis NC, Choi JD, Malim MH. 2002 Aug 8. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. In Nature 418(6898):646-50.
Sheehy AM, Gaddis NC, Choi JD, Malim MH. 2002 Aug 8. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein [abstract]. In Nature 418(6898):646-50. PubMed database < "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed">. Accessed 2006 Sept. 10.
UniProt. 2006 Sept. 5. UniProtKB Entry: Q9HC16.<http://www.pir.uniprot.org/cgi-bin/upEntry?id=Q9HC16>.Accessed 2006 Sept. 10.
Wiegand HL, Doehle BP, Bogerd HP, Cullen BR. 2004 Jun 16. A second human antiretroviral factor, APOBEC3F, is suppressed by the HIV-1 and HIV-2 Vif proteins [abstract]. In the EMBO Journal 23(12):2451-8. PubMed database< "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed" >. Accessed 2006 Sept. 10.
Yu X, Yu Y, Liu B, Luo K, Kong W, Mao P, Yu XF. 2003 Nov 7. Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex [abstract]. In Science 302(5647):1056-60. PubMed database < "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed">. Accessed 2006 Sept. 10.
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This page was created by Erin Zwack. Comments and questions are welcome.