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Human Immunodeficiency Virus 1
(HIV-1)

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Origin

The analysis of two archival HIV-positive samples collected in 1959 and 1960 on territory of the Democratic Republic of the Congo (previously Zaire) showed that at that time the group M viruses had already diversified significantly suggesting that they had been evolving in humans since 1902–1921.

In Africa, many species of indigenous nonhuman primates are naturally infected with related lentiviruses. Primates and the viruses co-evolved for very long time and as a result of mutual adaptations infections do not usually lead to AIDS-lile conditions despite of high plasma viral loads and sustained viral evolution.

Molecular phylogeny studies reveal that HIV-1 evolved from a strain of simian immunodeficiency virus, SIVcpz, within a particular subspecies of the chimpanzee (Pan troglodytes troglodytes). HIV-2 originated from SIVsm of sooty mangabeys (Cercocebus atys). Because SIV is a bloodborne pathogen and is also present in cells of mucous epithelium, humans could have been exposed to SIV on many occasions through bites, scratches, and wounds during hunting or other activities that involve monkeys and apes. The virus might have crossed primate-human barrier multiple times and at least on three separate occasions it was able to establish itself in the human organism at levels sufficient to become transmissible within the local human population resulting in three distinct phylogenetic lineages: M (Major, Main), N (New, Non-M, Non-O), and O (Outlier). O and N viruses are not pandemic. Thus, among the three SIVcpz ancestors of HIV-1 that have successfully crossed to humans, only one has given rise to the global AIDS pandemic: HIV-1 group M with subtypes A to K. Elegant field and phylogenetic studies determined that HIV-1 groups M and N (New) arose from geographically distinct chimpanzee populations in Cameroon however epicenter of human infections occured probably in Congo-Kinshasa (Zaire), Rwanda and Burundi. The origin of group O remains to be identified, but given the location of human cases, cross-species transmission may have occurred in neighboring Gabon. Group O viruses are most closely related to viruses infecting gorillas, and studies suggest that the gorillas acquired viruses from chimpanzees. are also the origin of infection of these gorillas. Similar to HIV-2, HIV-1 group O viruses are known to be naturally resistant to non-nucleoside RT (reverse transcriptase) inhibitors (NNRTs). Only a few cases of group N infections have been identified, and these were in patients from Cameroon.

Three hypotheses of global pandemic exist:

  1. The virus was transmitted to humans in the 1800s or early 1900s. It then would have remained isolated in a small, local human population until about 1930s, when it began spreading to other human populations and to diversify (Transmission Early Hypothesis).
  2. The virus was transmitted from chimpanzees to humans around 1930, and immediately began to spread and diversify in human populations (Transmission Causes Epidemic Hypothesis).
  3. Multiple strains of SIV were transmitted from chimpanzees to humans in the 1940s or 1950s (Parallel Late Transmisson Hypothesis).

It has been suggested that parallel transmission could have occured through oral poliovirus vaccinations adminestered in Central Africa between 1957 and 1960. Poliovirus was cultured in chimpanzee kidney cells that could have been contaminated with multiple SIVs. This hypothesis, however, does not withstand close scrutiny.

SIV cross species transmission models

Important adaptations have been necessary for the virus to acquire the ability to be efficiently transmitted. Since its emergence, HIV-1 group M has diverged into numerous clades or subtypes (A to K) as well as circulating recombinant forms (CRFs). CRFs have segments of the genome derived from more than one subtype. The highest diversity of HIV remains in west-central Africa, the region where HIV originated. Despite the potential for divergent viruses to spread, only a few viruses have successfully expanded with 90% of the epidemic comprising of just four subtypes (A, B, C and D) and two CRFs (CRF01_AE and CRF02_AG). Currently, subtype C, subtype A, and CRF02_AG together account for majority of thousands of new infections that occur daily worldwide. Historically, many more viruses should have been emerged from Africa but failed establish themselves within transmission networks, or were of lower fitness which limited their dispersal.

The amino acid distances among different subtypes of HIV-1 group M reach approximately 25–30% in the Env gene sequence and 15% in the Gag gene sequence. The subtypes B and D are better considered as subsubtypes within a single subtype, however they have been designated as subtypes for historical reasons. To define a new subtype, subsubtype or CRF, the representative strains must be identified in at least three epidemiologically unlinked individuals. Three near full length genomic sequences are preferred, but two complete genomes with partial sequences of a third strain are sufficient to designate a new subtype, subsubtype or CRF.

Regarding HIV in the Americas, subtype B was the first to appear in the United States and the Caribbean and still remains the most prevalent (98.0%) throughout the region. One study demonstrated that the epidemic originated in Haiti around 1966 and within 5 years a single transmission event occurred that culminated in the subtype B epidemic in the US. The spread of AIDS from Kinshasa and Congo to Haiti can be explained by hundreds of educational technicians working there for UNESCO between 1960 and 1975. All were single and returned regularly on holiday to Haiti.

Distribution of HIV-1 subtypes

Group Subtype Distribution
Group Subtype Distribution
M A East and Central Africa
B North and South Africa, Europe, Asia, Oceania
C South and East Africa, India, Brazil
D Central Africa
F Central Africa, Romania, Latin America
G Central Africa, Taiwan, Russia
H Central Africa, Belgium
J Congo, Gambia, Sweden
K Cameroon
O   Cameroon, Gabon, France
N   Cameroon

The most prevalent HIV-1 genotypes are subtypes C (47%), A (27.2%), B (12.3%), D (5.3%) and CRF01_AE (3.2%).

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HIV-1 classification

During the AIDS pandemic, it has become clear that host genetic differences between infected individuals as well as between viral species affect the susceptibility or resistance to the disease, revealing a clinical spectrum of rapid, intermediate, or slow progression or, more rarely, nonprogression to AIDS within infected populations.

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Literature

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