Two Major Lineages Of The Hiv Retrovirus Biology Essay

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What we have now come to know as HIV-1 was majorly identified in groups of male homosexuals and intravenous drug users in urban towns and cities in the United States. Clusters of male individuals were all presenting with various, yet similar symptoms, primarily pneumocystis pneumonia, cytomegalo virus, lymphadenopathy, kaposi's sarcoma and candidiasis(Gallo and Montagnier 2003). A report in 1981 for the center of disease control highlighted several cases of pneumocystis pneumonia in homosexual men living in los angelis(Gallo and Montagnier 2003). The sharp increase in case number lead to the adoptment of the term GRID or gay related immune deficiency, what we call AIDS today and defines the collective diseases associated with HIV and its progression(Gallo and Montagnier 2003). Heamophiliacs were also identified as a succeptable risk group in the early 1980's, and a race between American and Parisian scientists was initialised to try to identify the causative agent. The joint efforts of the laboratories of Robert Gallo at the national institute of health in the US and Luc montagnier at the Pasteur institute in Paris led to the isolation of the causitative virus and demonstration that the virus caused AIDS(Gallo and Montagnier 2003). A debate raged on between the two scientists over the name of the causitative virus settling on a compromise, HIV. Although the virus was identified in 1983, pre existing samples from the early 20th century show that HIV has infected humans, historically (Zhu, Korber et al. 1998). Specifically a sample taken from an African man who died in 1959 of a mysterious illness tested positive for HIV Evdence suggests that HIV reached pandemic proportions around 1969 (Zhu, Korber et al. 1998, Hillis 2000, Walker, Grassly et al. 2004) . Figure two shown below illustrates the time encapsulating the discovery of what we now call HIV and important discoveries and their progression.

Tackling theories, bushmeat and epidemic emergence

Numerous theories have been proposed in an attempt to explain the origin of the HIV-1 virus, responsible for the world wide pandemic. Perhaps the most substantial and disproved theory was that the virus originated from contaminated oral polio vaccine(Worobey, Santiago et al. 2004). Supporters of the theory argue that chimpanzees in the Kisangani region of the Democratic republic of congo were infected with SIVcpz and that they were used to culture OPV (in vivo) during the WHO attempts to eradicate polio myelitis across the globe(Worobey, Santiago et al. 2004). They held the opinion that the vaccine had been contaminated with SIVcpz and that this was the source for the current HIV-1/AIDS pandemic(Worobey, Santiago et al. 2004). Research in 2004 refuting the theory, finally put this theory to rest(Worobey, Santiago et al. 2004). By molecularly characterising and surveying chimpanzees in the Kisangani region researchers were eventually able to isolate SIVcpz viral RNA from chimpanzees endemic in the region(Worobey, Santiago et al. 2004). Genome and RNA analysis showed that the endemic SIVcpz strain was highly divergent from HIV-1, coupled with the wealth of data suggesting that HIV-1 emerged before opv trials were initiated, the opv theory can now be conclusively discounted as the cause of HIV-1 and specifically HIV-1 group M(Worobey, Santiago et al. 2004). Figure three shows a constructed phylogenetic tree for nef/gp41 sequences , illustrating that the Siv cpz DRC1 strain is distinct and highly divergent from the SIVcpz implicated in resultant HIV-1 infections(Worobey, Santiago et al. 2004).

Other theories of a less laudable, more conspiracy based origin for the HIV virus include the apparent splicing of Visna and HTLV-1 virus by the US military for population control of those with African descent(Klonoff and Landrine 1999, Libbey 2003). Some religious groups argue that HIV is a form of divine retribution sent by god to punish those most promiscuous(Somlai, Heckman et al. 1997). Such theories have no scientific evidence to support them have since been discredited, just like the theory that HIV does not cause aids(Blattner, Gallo et al. 1988).

The most plausible theory for the origins of the HIV-1 virus, its current pandemic proportions and its groups is that a cross species transmission event of a similar virus either SIVgor or SIV cpz (depending on the group of HIV-1) from primates, infected human populations(Hillis 2000, Peeters, Courgnaud et al. 2002, Rambaut, Posada et al. 2004, Sharp and Hahn 2011). The wealth of current evidence supports this to the extent of it being fact; however the question of how the virus came to enter human populations and its initial mode of transmission has not yet been fully ascertained. Currently the majority of evidence points towards bushmeat as being the vector of SIV transmission into the human population for the majority of current HIV-1 cases(Hillis 2000, Peeters, Courgnaud et al. 2002, Rambaut, Posada et al. 2004, Sharp and Hahn 2011). Bushmeat is wild meat , specifically used to describe wild animal's killed for food in western and centeral Africa. Primates such as monkeys and gorillas in this region are often hunted for meat, and as they have been and still are a source of SIV, it is thought that consumption and ritualistic use of Bushmeat coupled with blood to blood infection from butchery is the major source of SIV zoonosis into the human population resulting in HIV-1 groups M,N and O(Peeters, Courgnaud et al. 2002). A study in 2002 in Cameroon demonstrated that around 20 percent of primate bushmeat was infected with SIV, supporting the evidence suggesting that Bushmeat is the primary source of SIV infection in humans which can result in HIV (SIVcpz/SIVgor) (Peeters, Courgnaud et al. 2002) .

Another theory that is coupled with the bushmeat or "hunter theory" is that the wide spread use of syringes by African health officials to administer medicines to multiple individuals, using the same syringe with little sterilisation In between resulted in infection, during the 1950's(Chitnis, Rawls et al. 2000, Peeters, Courgnaud et al. 2002). This could have resulted in SIV transmissions from person to person, allowing the virus to mutate in a human population, resulting in HIV.

Other theories focussing on the emergence of HIV in human populations suggest that urbanisation as well as social changes in Africa lead to increased spread and more widespread emergence of HIV in the population.The theory proposed by prominent proffesors Beatrice Hahn and Paul Sharp, suggests that due to colonisation, formations of cities, towns and a movement away from secular tribes; sexual promiscuity increased (Sharp, Bailes et al. 2001, Peeters, Courgnaud et al. 2002, de Sousa, Mueller et al. 2010). This increase in promiscuity, coupled with new infrastructure and wide spread travel is thought to have largely led to the epidemic emergence of HIV. Phylogenetic evidence, dating the origins of HIV-1 groups M and O coinsides with the establishment of major colonial cities and infrastructure in central Africa(Korber 2000).Figure four shows the rate of population increase in kinsasha and bordering Brazzaville during colonialism (1906-1968), the establishment of transport links and cities, lead to increased migration and settling of families. The population explosion correlates well with the location and date of the proposed HIV-1 origins(Chitnis, Rawls et al. 2000).

Another theory known as the "Heart of darkeness" theory proposed by amit chitins, Diana rawls and Jim moore also suggest that HIV emerged due to social and economic changes with respect to colonialism, specifically in French equatorial Africa where harsh labouring conditions were rife, and bushmeat was a common staple food(Chitnis, Rawls et al. 2000). The heart of darkeness theory ties in with that of social change and urbanisation, as well as wide spread use of unstelisied needles to administer medicines and vaccines(Chitnis, Rawls et al. 2000, Marx, Alcabes et al. 2001).


Dating the source of HIV-1 transmission

Although what we now know as HIV-1 was only identified in the 1980's, phylogenetic evidence suggest's origins well before then. Indeed many independent HIV lineages were already circulating in African populations(Zhu, Korber et al. 1998, Vidal, Peeters et al. 2000, Bartolo, Rocha et al. 2009). To reiterate groups M N and O all represent separate lineages of HIV-1, from SIV infection's in p.t.troglodytes, which will be detailed later. It is also clear that the first cases of HIV-1 were likely to be in west and central Africa, as a result of sequence comparisons of HIV-1 gag, pol and env genes. But when did this occur? Using molecular clock analysis to determine when lineages split, assuming a constant rate of mutation and using the dates of known molecular divergences Korber and colleges showed that the last common ancestor of HIV-1 group M was in existence around 1915-1941(Hillis 2000, Korber 2000).Specifically analysis of HIV-1 group M, gag and env genes both gave the same result. It is important to note that this date range represents the existence of the last common ancestor and not the date of cross species transmission(Hillis 2000). As david hills writes about in his article " origins of HIV" this information gives rise to three hypothesis for initial transmission of HIV -1 group M the most well supported termed " transmission early" tieing in with the heart of darkness and socio economic and urbanisation theories of HIV origins(Hillis 2000). Suggesting that political, social and economic changes in central and wester Africa accounted for the initial spread of the virus and its diversity in human populations

The origins of the HIV-1 pandemic- Group M

It is consensually agreed, and demonstrated by HIV/AIDS global statistics that HIV-1 Group M is responsible for the majority of HIV/AIDS cases across the world, and that HIV-2 is mainly restricted to west and central Africa(Gao, Bailes et al. 1999). It therefore seems plausible to focus on the origins of HIV-1 Group M when describing the pandemic, as well as the individual zoonotic event resulting in establishment of Group M. Group M encapsulates several subtypes of infectious HIV, including many clades majorly endemic to distinct geographical populations, as well as circulating recombinant forms, established due to recombinantion of viruses of different subtypes in vivo. However it is clear that all of these clades / subtypes emerged from one ancestreal strain of HIV-1(Vidal, Peeters et al. 2000).

Although we now know that HIV-1 is of chimpanzee origin, it has only recently been confirmed that this is the case(Gao, Bailes et al. 1999, Sharp and Hahn 2011). Thanks to ape population studies in recent years, determining SIVcpz infection in P. t. schweinfurthii in eastern Africa, and p.t.troglodytes in central Africa, it has now been established beyond reasonable doubt that the source or reservoir of HIV-1 group M is the siv cpz infected chimpanzee species pan troglodytes in central africa. P. t. schweinfurthii Sivcpz virus shows considerable genetic diversity from the virus found in p.ttroglodytes approximately 30-50 percent difference in protein sequences of Gag Pol and Env genes, and considerable diversity from HIV-1 groups M, N and O compared with SIV infected p.t.troglodytes(Gao, Bailes et al. 1999, Hillis 2000, Santiago, Rodenburg et al. 2002, Sharp and Hahn 2011). HIV-1 subtypes M,N and O infections are only closely related to Siv cpz in p.t.troglodytes thus suggesting that this is the species of chimpanzee responsible for the current world wide pandemic. Siv infected p.t.troglodytes reside in central Africa, and P. t. schweinfurthii, eastern Africa, allowing determination of the geographic source of HIV-1.


Group P, the mistery of frequency and tetherin.

In the last few years a new subtype of HIV-1 has become apparent. Group P, detected in a small number of patients originating from Cameroon, was detected by HIV virologists(Sauter, Hue et al. 2011). Upon isolation of the virus and phylogenetic analysis, researchers found that unlike HIV-1 M,N and O subtypes, the P subtype is most similar to the species SIVgor, than SIVcpz(Gupta and Towers 2009), suggesting a gorilla origin for the virus. Data suggests that HIV-1 Group P entered the human population between 1845 and 1989(Gupta and Towers 2009). What has still remained a mystery is the fact that HIV-1 N,O and P subtypes is considerably less prevealent than group M across the globe , when comparably ancestry dating differences are insignificant. This suggests that Group M is more infectious, or that it has selective advantages over the N,O and P groups(Gupta and Towers 2009, Sauter, Hue et al. 2011).

Tetherin, a protein induced by an interferon response works to prevent the release of HIV-1.Several mechanisms have been in a bid to explain these interactions(Gupta and Towers 2009). Tetherin's may hold the key to explaining the low global frequency of HIV-1 infections in subtypes N,O and P. Research by sauter and colleagues in 2009 detailed that HIV-1 group M had adapted its Vpu protein allowing sucsessfull release of virions, from infected cells(Gupta and Towers 2009). This adaptation allowed the Vpu protein to antagonize tetherin and perhaps plays a large role in explaining why HIV-1 group M is so prevealent(Gupta and Towers 2009). Research into groups O and P suggest that there viruses could not antagonize tetherin successfully, possibly helping to explain the lower prevealence of these infections globally when compared with group M(Gupta and Towers 2009). In research into Group N, more sketchy comparisons were drawn. Due to the rarity of group N infection, only three individuals tetherin activity was tested, In one individual tetherin was antagonised well, in the other two there was little antagonistic activity(Gupta and Towers 2009). An area in which there has been little research into is the genetics of the tetherin protein. Due to the low frequency of group n, o and P infection it is plausible that some individuals with these infections may have amino acid changes or mutations in there tetherin protein which make them more susceptible to group N, O or P infection. This hypothesis helps to complete the explanation for largely differing infection rates between the groups and is possibly a further avenue of research for virologists, although there is little evidence to support this to date.


In conclusion the origins of the HIV-1 Pandemic is likely to have started due to cross infection of SIVcpz from p.troglodytes, in central Africa, resulting in the establishment of HIV-1 group M (pandemic strain). This resultant zoonosis is likely to have occurred due to consumption, ritualistic use or blood to blood (hunter theory) transmission from bushmeat (p.troglodytes) to humans. HIV-1 groups M, N and O represent three events of zoonosis which could encapsulate each other. One of these hypothesis. It is clear that over time the resultant SIVcpz infection changed to become HIV, disease causing in human populations. In French equatorial Africa colonialism, contaminated needles, increased promiscuity and better infrastructure may also be responsible for the initial spread of HIV-1, as well as some circulating recombinant forms of the virus.

Phylogenetic data, and standardized sequence data show that the common ancestor to the Sivcpz, responsible for the HIV-1 pandemic strain (M) originated between 1915 and 1941 and disproves the contaminated oral polio vaccine theory for the origin of HIV-1.

HIV-1 groups N,O and P may have very low frequency of infection/ prevealence due to viral protein interactions between them and the human protein tetherin, which works to prevent virion release. This provides an explanation for a question that has puzzled scientists for well over a decade.


Groups NOP??

Group M - current research and spread from first theoretical infection

Siv from chimps and gorillas

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