Reviewing "The evolution of HIV-1 and the origin of AIDS" by Paul Sharp and Beatrice H. Hayn

If you are interested in reading the paper that correlates to these questions and following along please go to this link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935100/

1. What is phylogeography? How were the authors able to use phylogenetics and phylogeography to localize the origin of HIV strains?

Phylogeography is the study of the genetic and geographic structure of populations and species. Phylogeography generally uses genetic information to examine genealogical history and patterning within species and populations.

The authors were able to localize the origin of the HIV strain through a series of tests in various primates to determine which species had been infected and which carried viruses that closely resembled HIV (Types O, M and N). To begin, the authors first tested a wide range of primates and began identifying SIV’s (simian immunodeficiency virus), a 1920 test had shown M type HIV in Kinshassa, Democratic Republic of Congo and this is where they began looking for similar SIVs. The first break through was in the discovery of SIVcpz in 1989, this chimpanzee SIV was very similar to HIV-1 which is the most prevalent type of HIV and thus of the most interest to the authors. After the discovery of the SIVcpz there was a huge push to test as many chimpanzees as possible to learn more about the origin of the species, this push only resulted in a couple more cases being found. In 2002, a new method of testing was developed and allowed fecal samples of wild chimpanzees to be analyzed; through these tests it was found that SIVcpz was very prevalent among the central and eastern chimpanzees. The similarity and prevalence of SIVcpz in these subspecies of chimpanzees shows that they are the source for HIV-1.

Once all of this data was gathered they were able to add the SIV and HIV strains into a phylogenetic tree and see how the strains are related to each other. Using this phylogenetic tree, they identified that the HIV type M and N were transferred directly from the chimpanzees. The HIV type O, however required several cross species transfers to come to humans. The SIVcpz was first transferred to gorillas before coming to humans. These crosses were supported by looking at the mutations of SIV and HIV in specific geographic locations. These locations line up with the intra-species crosses suggested in the phylogenetic tree.

2. How do they know that most HIV transmissions are intraspecific? Explain.

The multiple strains of SIVs were characterized from a single species; they generally formed a monophyletic clade, which indicated that the majority of transmissions are intraspecific.

3. What do the env, vpu, and nef genes code for in HIV? Would you then expect high levels of mutation rates to be tolerated in these genes?

The env gene codes for the env viral protein. This protein assists in the formation of the viral envelope. It is also common for retroviruses, and helps retroviruses target and attach to cells. In addition, it helps the virus gain access to the cell membrane of a target cell. Vpu is a protein that is involved in the degradation of CD4. It also assists in the virion release from the membrane of infected cells. Nef is a protein encoded by primate lentivirsuses. It assists in manipulating the host cell’s machinery, which ultimately helps with infection. High levels of mutation rates would not be tolerated in these genes as they code for proteins that provide essential functions for the HIV virus to infect cells.

4. Apply Darwin’s postulates to the adaptation of the recombinant virus to the human host population.

1. The individuals within a population differ from one another.

HIVs and SIVs interact with many host proteins. Many of those host proteins have diverged since the common ancestor of old world monkeys and apes. There is variance within the HIV population.

2. The differences are, at least in part, passed from parent to offspring.

When inside of a host, HIV replicates itself and passes it’s genetic information on to its offspring.

3. Some individuals are more successful at surviving and reproducing than others.

Tetherin is a mammalian protein with antiviral activity by preventing the release of the virus into the cytoplasm. Only SIV or HIV-1 that are resistant to tetherin survive and reproduce.

4. Individuals with more favorable adaptations are more likely to survive and reproduce.

SIVcpz uses the Nef protein to counteract tetherin, while HIV-1 uses Vpu. This is because human tetherin has diverged from the chimpanzee protein. As a result, SIVcpz Nef protein is not active against human tetherin. This would have placed strong selection pressure on HIV-1, which resulted in the reaquisition of anti-tetherin activity by Vpu. HIV-1 viruses that were active against human tetherin would be more successful at surviving and reproducing. 

5. What evidence does this study provide that we share an immediate common ancestor with Pan troglodytes?

The study states that humans and Pan troglodytes share very similar gene sequences. The differences between the two are at less than two percent of all nucleotides. The evidence that they come from a common ancestor can be seen with how easily the SIVcpz transferred to humans. 

6. On the next page you will find a figure from Science entitled “Application and Accuracy of Molecular Phylogenies” (Hillis et al. 1994; Vol. 264: 671-677). In the study referenced, the authors considered the allegations of 7 patients (A-G) that they had contracted HIV from their dentist. Were their allegations correct? Describe how the authors might have generated this tree.

Yes, the dentist did transmit HIV to his patients. HIV tends to have an A to G nucleotide base change, but there are other nucleotide base changes that can occur. The researchers probably looked at those other changes and documented which ones these patients had.  Though, they also took into account all other transversions and transitions because they need to have a thorough phylogenic tree.Taking into account all the possible changes, they might have looked at the number of times those specific nucleotide base changes occurred. The researchers would then take into account which of these changes was most similar to the that of the dentist.