HIV, the virus that causes AIDS can be grouped into two households: HIV-1 and HIV 2. The beginnings of HIV-2 have been established as cross species transmittal of a virus infecting a distinguishable monkey species called Simian immune lack virus, to human populations. This thesis analyses current research around the beginnings of HIV-1 specifically the strains responsible for the bulk of infections worldwide, termed group M. Research has shown that group M has originated due to traverse species transmittal of a Simian immune lack virus from a common Pan troglodytes species in cardinal Africa. Familial comparings every bit good as comparings of cistron administration support these findings and besides suggest that the last common ascendant of this HIV-1 group existed between 1915 and 1941. I besides a focal point on the history of the HIV/AIDS find every bit good as theories explicating the cross species transmittal, such as monkey to human, blood to blood transmittal and an account of theories, explicating how HIV has become so diverse, in add-on to the alterations in infection rates of different HIV-1 groups.
Phylogenetic Comparisons and similarities in cistron administration between SIVcpz in Pan troglodytes Troglodytess and HIV-1 ( specifically group M ) show that they are closely related, proposing HIV-1 group M originated due to transmittal of SIVcpz from Pan troglodytes Troglodytess, dating the last common ascendant between 1915-1941. Group M, responsible for the universe broad pandemic, like other HIV-1 strains is likely to hold arisen due to ingestion or blood to blood transmittal ( hunter theory ) of bushmeat from Pan troglodytes Troglodytess. Evidence besides supports this theory for the constitution of other zoonotic groups of HIV-1, specifically N and O. Research elucidates to a gorilla beginning for the HIV-1 P strain, discovered in 2009 in a female of Cameroonian beginning. Throughout this thesis I discuss the history of the HIV-1 pandemic, from its find, theories of its beginning, including, the contaminated OPV theory, theories explicating its spread such as colonialism, development in substructure and the bosom of darkness theory in add-on to the most supported bushmeat/hunter theory. Besides discussed are the beginnings of HIV-1 group P and the differential frequence of HIV-1 group infections.
Two major line of descents of the retrovirus, HIV, cause AIDS, HIV-1 and HIV-2 ( Gao, Bailes et Al. 1999 ) . The beginnings of HIV-2, much less common and by and large restricted to western Africa, have been established as a zoonotic disease of SIVsm from coal-black mangabeys to the human population ( Gao, Bailes et Al. 1999, Lemey, Pybus et Al. 2003 ) . A wealth of phyletic, viral protein sequence similarity and genome similarity surveies support these decisions every bit good as several epidemiological surveies ( Gao, Bailes et Al. 1999, Bartolo, Rocha et Al. 2009 ) . The beginnings of HIV-1 have besides been established ( Gao, Bailes et Al. 1999, Sharp and Hahn 2011 ) . HIV-1 is responsible for the bulk of AIDS instances across the Earth and due to high mutant rates during reproduction of the RNA genome every bit good as laminitis effects, this has resulted in the development of genetically distinguishable subtypes.
HIV-1 is categorised into four groups, group M ( major group ) is believed to be responsible for 90 per centum of HIV/AIDS instances worldwide and hence will be the major focal point of this thesis ( Hemelaar, Gouws et Al. 2006 ) . Groups N, O and late P have besides been established, these groups represent separate transmittals of SIV ‘s to worlds ( Hillis 2000, Sauter, Hue et Al. 2011 ) . The chief group, group M is farther divided into subtypes based on epidemiology and sequence differences, group M besides encapsulates CRF ‘s, go arounding recombinant signifiers, the consequence of co-infection, recombination and spread of more than one subtype, those within the HIV-1 Group M sphere ( Vidal, Peeters et Al. 2000, Hemelaar, Gouws et Al. 2006 ) . Figure one shows the planetary distribution of HIV-1 Group M subtypes A-K and CRF ‘s along with their proposed geographical migration paths.
Figure 1. Proposed migration paths for the spread of HIV infection and planetary prevalence of HIV-1 groups, subtypes and CRF ‘s. Figure from: hypertext transfer protocol: //www.medscape.com/viewarticle/760844_4 [ last accessed 1st March 2013 ]
Detecting HIV: A historical position
What we have now come to cognize as HIV-1 was foremost identified in groups of male homophiles and endovenous drug users in metropoliss of the United States. In wellness Centres bunchs of cheery work forces were showing with assorted symptoms, chiefly pneumocystis pneumonia, cytomegalo virus, lymphadenopathy, kaposi ‘s sarcoma and moniliasis ( Gallo and Montagnier 2003 ) . A study in 1981 for the centre of disease control highlighted several instances of pneumocystis pneumonia in homosexual work forces populating in Los Angeles ( Gallo and Montagnier 2003 ) . The crisp addition in instance figure led to the adopting of the term GRID or homosexual related immune lack, what we call AIDS today ( Gallo and Montagnier 2003 ) .
Haemophiliacs were besides identified as a susceptible hazard group in the early 1980 ‘s, and a race between American and Parisian scientists was initialised to seek to place the causative agent. The joint attempts of the research labs of Robert Gallo at the national institute of wellness in the US and Luc Montagnier at the Pasteur institute in Paris led to the isolation of the virus and presentation that the virus caused AIDS ( Gallo and Montagnier 2003 ) . A argument ensued between the two scientists over the name of the virus settling on a via media, HIV. Although the virus was identified in 1983, pre bing samples from the early twentieth century show that HIV has infected worlds, historically ( Zhu, Korber et Al. 1998 ) . Specifically a sample taken from an African adult male who died in 1959 of a cryptic unwellness, tested positive for HIV. Epidemiologic surveies suggest 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 clip encapsulating the find of what we now know as HIV, of import events and their patterned advance.
Figure 2. Timeline of of import events environing the discovery/ designation of HIV and AIDS.
Undertaking theories, bushmeat and epidemic outgrowth
Numerous theories have been proposed in an effort to explicate the beginning of HIV-1, responsible for the universe broad pandemic. One such theory suggested that the virus originated from contaminated unwritten infantile paralysis vaccinum ( Hooper 2001 ) . Supporters of the theory argue that chimpanzees in the Kisangani part of the Democratic democracy of Congo were infected with SIVcpz were used to civilization OPV ( in vivo ) during the WHO attempts to eliminate infantile paralysis myelitis across the Earth ( Worobey, Santiago et Al. 2004 ) . They held the sentiment that the vaccinum had been contaminated with SIVcpz and that this was the beginning for the current HIV-1/AIDS pandemic. Research in 2004 rebuting the theory, eventually put this theory to rest ( Worobey, Santiago et Al. 2004 ) . By molecularly characterising and appraising Pan troglodytess in the Kisangani part research workers were finally able to insulate SIVcpz viral RNA from the fecal matters of endemic Pan troglodytess, non-invasively. Genome and RNA analysis showed that the endemic SIVcpz strain was extremely divergent from HIV-1, coupled with the wealth of informations proposing that HIV-1 emerged before OPV tests were initiated, the OPV theory can now be once and for all discounted as an account for the beginning of HIV-1 and specifically HIV-1 group M ( Worobey, Santiago et Al. 2004 ) . Figure three shows a constructed phyletic tree for Nef/gp41 sequences, exemplifying that the SIVcpz DRC1 strain is distinguishable and extremely divergent from the SIVcpz implicated in attendant HIV-1 infections.
Figure 3. Nef/gp41 Phylogenetic relatedness tree comparings of SIV ‘s and HIV-1.
Figure from: –
( Worobey, Santiago et Al. 2004 )
Other theories include the evident splice 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 spiritual groups argue that HIV is a signifier of godly requital sent by God to penalize those most promiscuous ( Somlai, Heckman et al. 1997 ) . Such theories have no scientific grounds to back up them have since been discredited, merely like the theory that HIV does non do AIDS ( Blattner, Gallo et Al. 1988 ) .
The most plausible theory for the beginnings of the four HIV-1 groups is that cross species transmission events of a similar virus, either SIVgor or SIVcpz ( depending on the group ) from Primatess, infected human populations ( Hillis 2000, Peeters, Courgnaud et Al. 2002, Rambaut, Posada et Al. 2004, Sharp and Hahn 2011 ) . However the inquiry of how the virus came to come in the human population and its initial manner of transmittal has non yet been to the full ascertained. Presently the bulk of grounds suggests bushmeat as the beginning of SIV transmittal into the human population for the bulk of current HIV-1 instances ( Hillis 2000, Peeters, Courgnaud et Al. 2002, Rambaut, Posada et Al. 2004, Sharp and Hahn 2011 ) . Bushmeat is the meat of wild animate being ‘s killed for nutrient. Primates such as monkeys and gorillas in western and cardinal Africa are frequently hunted and are still a beginning of SIV. It is thought that ingestion of bushmeat coupled with blood to blood infection from abattoir is the major beginning of SIV zoonotic disease into the human population ensuing in HIV-1 groups M, N and O ( Peeters, Courgnaud et Al. 2002 ) . A survey in 2002 in Cameroon demonstrated that around 20 per centum of archpriest bushmeat was infected with SIV, proposing that Bushmeat is the primary beginning of SIV infection in worlds which can ensue in HIV ( SIVcpz/SIVgor ) ( Peeters, Courgnaud et Al. 2002 ) .
Another theory that is coupled with the bushmeat or huntsman theory is that the broad spread usage of panpipes by African wellness functionaries lead to the rise of HIV. Disposable fictile panpipes were used to administrate medical specialties to multiple persons repetitively, with small sterilization In between, ensuing in HIV outgrowth around the 1930 ‘s ( Chitnis, Rawls et Al. 2000, Peeters, Courgnaud et Al. 2002 ) . This could hold resulted in SIV transmittals from individual to individual, leting the virus to accommodate to the human population, ensuing in HIV.
Other hypotheses focus on the outgrowth of HIV in the human population. They suggest that urbanization every bit good as societal alterations in Africa led to increased transmittal and more widespread outgrowth of HIV. The theory suggests that due to colonization, formations of metropoliss, towns and a motion off from secular folks ; sexual promiscuousness increased ( Sharp, Bailes et Al. 2001, Peeters, Courgnaud et Al. 2002, de Sousa, Mueller et Al. 2010 ) . This addition in promiscuousness, coupled with new substructure and broad spread travel is thought to hold led to the widespread outgrowth of HIV. Phylogenetic analysis by Korber, shows that the beginnings of HIV-1 groups M and O coincides with the constitution of major colonial metropoliss and substructure in cardinal Africa ( Korber 2000 ) . Figure four shows the rate of population addition in Kinshasa and surrounding Brazzaville during colonialism ( 1906-1968 ) , the constitution of conveyance links and metropoliss led to increased migration and subsiding of households. The population detonation correlates good with the location and day of the month of the proposed HIV-1 beginnings ( Chitnis, Rawls et Al. 2000 ) .
Figure 4. Population graph during the colonialism period 1906-1968 in Kinsasha and neighboring Brazzaville.
Figure from: – ( Chitnis, Rawls et Al. 2000 )
Another theory known as the “ Heart of darkness ” theory proposed by Amit Chitins et Al. ( 2000 ) besides suggests that HIV emerged due to societal and economic alterations with regard to colonialism, specifically in Gallic equatorial Africa where harsh, forced drudging conditions were rife, and bushmeat was a common basic nutrient ( Chitnis, Rawls et Al. 2000 ) . The bosom of darkness theory ties in with that of societal alteration and urbanization, every bit good as broad spread usage of unsterilised acerate leafs to administrate medical specialties and vaccinums ( Chitnis, Rawls et Al. 2000, Marx, Alcabes et Al. 2001 ) .
Dating the beginning of HIV-1 transmittal
Although HIV-1 was merely identified in the 1980 ‘s ; phyletic grounds suggests beginnings good before so. Indeed, many independent HIV line of descents were already go arounding in African populations ( Zhu, Korber et Al. 1998, Vidal, Peeters et Al. 2000, Bartolo, Rocha et Al. 2009 ) . To repeat groups M, N and O all represent separate line of descents of HIV-1, from SIV infection ‘s in Pan troglodytes Troglodytess although the beginnings of group O have non been to the full established and could arise from SIVgor. It is besides clear that the first instances of HIV-1 were likely to be in west and cardinal Africa, as a consequence of sequence comparings of HIV-1 joke, pol and env cistrons ( Gao, Bailes et Al. 1999, Keele, Van Heuverswyn et Al. 2006 ) . But when did this occur? Using molecular clock analysis to find when line of descents split, presuming a changeless rate of mutant and utilizing the day of the months of known molecular divergencies Korber and colleges showed that the last common ascendant of HIV-1 group M was in being around 1915-1941 ( Hillis 2000, Korber 2000 ) . Analysis of HIV-1 group M, joke and env cistrons both gave similar consequences. It is of import to observe that this day of the month scope represents the being of the last common ascendant and non the day of the month of cross species transmittal ( Hillis 2000 ) . As David Hills writes about in his article “ beginnings of HIV ” this information gives rise to three hypothesis ‘ for initial transmittal of HIV -1 group M, the most good supported termed “ transmittal early ” , ( see figure five ) ligature in with the bosom of darkness and socio economic and urbanisation theories of HIV beginnings ; Proposing that political, societal and economic alterations in cardinal and western Africa accounted for the initial spread of the virus and its diverseness in human populations.
Figure 5. Transmission early hypothesis, demoing diverging subtypes arising from one original line of descent
Figure adapted from: – ( Hillis 2000 )
The beginnings of the HIV-1 pandemic- Group M
HIV-1 Group M is responsible for the bulk of HIV/AIDS instances across the universe, HIV-2 is chiefly restricted to west and cardinal Africa ( Gao, Bailes et Al. 1999 ) . It hence necessary to concentrate on the beginnings of HIV-1 Group M when depicting the pandemic, every bit good as the single zoonotic event ensuing in its constitution. Group M encapsulates several subtypes of HIV, including many clades endemic to distinct geographical populations, every bit good as go arounding recombinant signifiers, established due to recombination of viruses of different subtypes in vivo. However it is clear that all of these clades/subtypes emerged from one hereditary strain of HIV-1 ( Vidal, Peeters et Al. 2000 ) .
We now know that pandemic HIV-1 is of Pan troglodytes beginning. ( Gao, Bailes et Al. 1999, Sharp and Hahn 2011 ) . Thankss to non invasive ape population surveies in recent old ages, finding SIVcpz infection in Pan troglodytes schweinfurthii in eastern Africa, and Pan troglodytes Troglodytess in cardinal Africa, it has now been established beyond sensible uncertainty that the beginning or reservoir of HIV-1 group M is the SIVcpz infected chimpanzee species Pan troglodytes Troglodytess. Surveies of antibodies in archpriest fecal matters have made this all possible every bit good as associating Pan troglodytes Troglodytess in southern Cameroon to the beginning of the pandemic ( Keele, Van Heuverswyn et Al. 2006 ) .
Pan troglodytes schweinfurthii SIVcpz virus shows considerable familial diverseness from the virus found in Pan troglodytes Troglodytess about 30-50 per centum difference in protein sequences of joke pol and env cistrons, and considerable diverseness from HIV-1 groups M, N and O compared with SIV infected Pan Troglodytess Troglodytess ( Gao, Bailes et Al. 1999, Hillis 2000, Santiago, Rodenburg et Al. 2002, Sharp and Hahn 2011 ) . Pandemic HIV-1 infections are merely closely related to SIVcpz in Pan troglodytes Troglodytess therefore proposing that this is the species of Pan troglodytes responsible for the current universe broad pandemic. SIV infected Pan troglodytes Troglodytess in cardinal Africa, and Pan troglodytes schweinfurthii, eastern Africa, allow finding of the geographic beginning of HIV-1.
Group P, the enigma of frequence and tetherin.
In the last few old ages a new line of descent of HIV-1 has become evident. Group P, detected in a little figure of patients, was found by HIV virologists in a Cameroonian female ( Plantier, Leoz et Al. 2009 ) . Upon isolation of the virus and phyletic analysis research workers found that unlike HIV-1 M, N and O, the P group is most similar to SIVgor than SIVcpz ( Plantier, Leoz et Al. 2009 ) , proposing a gorilla beginning 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 enigma is the fact that HIV-1 N, O and P groups are well less prevailing than group M across the Earth, when comparably, lineage dating differences are undistinguished. This suggests that group M is more infective, 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 the human interferon response, works to forestall the release of HIV-1. Several proposed mechanisms have been put frontward to explicate these interactions ( Gupta and Towers 2009 ) . Tetherin ‘s may keep the key to explicating the low planetary frequence of HIV-1 infections in subtypes N, O and P. Research by Sauter and co-workers in 2009 detailed that HIV-1 group M had adapted its Vpu protein leting successful release of HIV virions from septic cells. This version allowed the Vpu protein to antagonise tetherin and possibly plays a big function in explicating why HIV-1 group M is so prevailing ( Gupta and Towers 2009 ) . Research into groups O and P suggest that there viruses could non antagonise tetherin successfully, perchance assisting to explicate the lower prevalence of these infections globally when compared with group M ( Gupta and Towers 2009 ) . In research into group N and tetherin ‘s research was less conclusive. Due to the rareness of group N infection, merely three persons tetherin activity was tested, In one single tetherin was antagonised good, in the other two there was small counter activity ( Gupta and Towers 2009 ) . Research published today ( 20/3/2013 ) has shown that merely alterations in the transmembrane sphere of HIV-1 Vpu is “ sufficient to confabulate anti-tetherin activity to SIVcpz and SIVgor Vpu proteins ” , ( Kluge, Sauter et Al. 2013 ) .
An country in which there has been small research into is the genetic sciences of the tetherin protein. Due to the low frequence of group N, O and P infections, it is plausible that some persons with these infections may hold amino acerb alterations or mutants in there tetherin protein which make them more susceptible to group N, O or P infection. This hypothesis provides an account for the mostly differing infection rates between the groups.
The beginnings of the HIV-1 Pandemic started due to traverse infection of SIVcpz from Pan troglodytes Troglodytess, in cardinal Africa, ensuing in the constitution of HIV-1 group M ( pandemic strain ) ( Gao, Bailes et Al. 1999, Sharp and Hahn 2011 ) . This zoonotic disease event is likely to hold occurred due to ingestion, or blood to blood ( hunter theory ) transmittal from bushmeat ( Pan troglodytes Troglodytess ) to worlds ( Peeters, Courgnaud et Al. 2002 ) . HIV-1 groups M, N, O and P represent four independent zoonotic events. It is clear that over clip the human SIVcpz infection adapted to go HIV, disease-causing in the human population. In Gallic Equatorial Africa colonialism, contaminated acerate leafs, increased promiscuousness and better substructure may hold besides been responsible for the spread of HIV-1.
Phylogenetic informations, and standardized sequence informations show that the common ascendant to the SIVcpz, responsible for the HIV-1 pandemic strain ( M ) originated between 1915 and 1941 ( Zhu, Korber et Al. 1998, Korber 2000 ) .HIV-1 groups N, O and P may hold really low frequence of infection / prevalence due to viral protein interactions between them and the human protein tetherin, which works to forestall virion release ( Gupta and Towers 2009, Sauter, Hue et Al. 2011 ) . As many archpriest species are infected with SIV there may be concern about the possibility of new zoonotic disease originating with the potency for new pandemic strains. However host limitation factor ‘s every bit good as SIV differences in Primatess coupled with the demand for consecutive transition and adaptative mutant ‘s will supply a functional barrier against future cross species transmittals ( Sharp and Hahn 2011 ) .