Acquired Immune Deficiency Syndrome (AIDS) was first recognized as a new disease in 1981 when increasing numbers of young homosexual men succumbed to unusual opportunistic infections and rare malignancies (CDC 1981; Greene 2007). A retrovirus, now termed human immunodeficiency virus type 1 (HIV-1), was subsequently identified as the causative agent of what has since become one of the most devastating infectious diseases to have emerged in recent history (Barre-Sinoussi et al. 1983; Gallo et al. 1984; Popovic et al. 1984). HIV-1 spreads by sexual, percutaneous, and perinatal routes (Hladik and McElrath 2008; Cohen et al. 2011); however, 80% of adults acquire HIV-1 following exposure at mucosal surfaces, and AIDS is thus primarily a sexually transmitted disease (Hladik and McElrath 2008; Cohen et al. 2011). Since its first identification almost three decades ago, the pandemic form of HIV-1, also called the main (M) group, has infected at least 60 million people and caused more than 25 million deaths (Merson et al. 2008). Developing countries have experienced the greatest HIV/AIDS morbidity and mortality, with the highest prevalence rates recorded in young adults in sub-Saharan Africa (http://www.unaids.org/). Although antiretroviral treatment has reduced the toll of AIDS- related deaths, access to therapy is not universal, and the prospects of curative treatments and an effective vaccine are uncertain (Barouch 2008; Richman et al. 2009). Thus, AIDS will continue to pose a significant public health threat for decades to come.

Ever since HIV-1 was first discovered, the reasons for its sudden emergence, epidemic spread, and unique pathogenicity have been a subject of intense study. A first clue came in 1986 when a morphologically similar but antigenically distinct virus was found to cause AIDS in patients in western Africa (Clavel et al. 1986). Curiously, this new virus, termed human immunodeficiency virus type 2 (HIV-2), was only distantly related to HIV-1, but was closely related to a simian virus that caused immunodeficiency in captive macaques (Chakrabarti et al. 1987; Guyader et al. 1987). Soon thereafter, additional viruses, collectively termed simian immunodeficiency viruses (SIVs) with a suffix to denote their species of origin, were found in various different primates from sub-Saharan Africa, including African green monkeys, sooty mangabeys, mandrills, chimpanzees, and others (Fig. 1). Surprisingly, these viruses appeared to be largely nonpathogenic in their natural hosts, despite clustering together with the human and simian AIDS viruses in a single phylogenetic lineage within the radiation of lentiviruses (Fig. 2). Interestingly, close simian relatives of HIV-1 and HIV-2 were found in chimpanzees (Huet et al. 1990) and sooty mangabeys (Hirsch et al. 1989), respectively. These relationships provided the first evidence that AIDS had emerged in both humans and macaques as a consequence of cross-species infections with lentiviruses from different primate species (Sharp et al. 1994). Indeed, subsequent studies confirmed that SIVmac was not a natural pathogen of macaques (which are Asian primates), but had been generated inadvertently in US primate centers by inoculating various species of macaques with blood and/or tissues from naturally infected sooty mangabeys (Apetrei et al. 2005, 2006). Similarly, it became clear that HIV-1 and HIV-2 were the result of zoonotic transfers of viruses infecting primates in Africa (Hahn et al. 2000). In this article, we summarize what is known about the simian precursors of HIV-1 and HIV-2, and retrace the steps that led to the AIDS pandemic.



Figure 1.

Origins of human AIDS viruses. Old World monkeys are naturally infected with more than 40 different lentiviruses, termed simian immunodeficiency viruses (SIVs) with a suffix to denote their primate species of origin (e.g., SIVsmm from sooty mangabeys). ...





Figure 2.

Phylogeny of lentiviruses. The evolutionary relationships among Pol sequences (∼ 770 amino acids) derived from various mammalian lentiviruses; host species are indicated at the right. Exogenous viruses are depicted in black, with HIV-1, HIV-2, ...

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Origins of HIV and the AIDS Pandemic

Human immunodeficiency virus type 1 (HIV-1), the cause of human acquired immunodeficiency syndrome (AIDS), is a zoonotic infection of staggering proportions and social impact. Yet uncertainty persists regarding its natural reservoir. The virus most closely related to HIV-1 is a simian immunodeficiency virus (SIV) thus far identified only in captive members of the chimpanzee subspecies Pan troglodytes troglodytes. Here we report the detection of SIVcpz antibodies and nucleic acids in fecal samples from wild-living P. t. troglodytes apes in southern Cameroon, where prevalence rates in some communities reached 29 to 35%. By sequence analysis of endemic SIVcpz strains, we could trace the origins of pandemic (group M) and nonpandemic (group N) HIV-1 to distinct, geographically isolated chimpanzee communities. These findings establish P. t. troglodytes as a natural reservoir of HIV-1.

/pdf/chimpanzee-reservoirs-of-pandemic-and-nonpandemic-hiv-1-h343yamdqa.pdf

Chimpanzee reservoirs of pandemic and nonpandemic HIV-1.

Globally, human immunodeficiency virus–type 1 (HIV-1) is extraordinarily variable, and this diversity poses a major obstacle to AIDS vaccine development. Currently, candidate vaccines are derived from isolates, with the hope that they will be sufficiently cross-reactive to protect against circulating viruses. This may be overly optimistic, however, given that HIV-1 envelope proteins can differ in more than 30% of their amino acids. To contend with the diversity, country-specific vaccines are being considered, but evolutionary relationships may be more useful than regional considerations. Consensus or ancestor sequences could be used in vaccine design to minimize the genetic differences between vaccine strains and contemporary isolates, effectively reducing the extent of diversity by half.

https://science.sciencemag.org/content/sci/296/5577/2354.full.pdf

Diversity considerations in HIV-1 vaccine selection.

Human immunodeficiency virus type 1 (HIV-1) sequences that pre-date the recognition of AIDS are critical to defining the time of origin and the timescale of virus evolution. A viral sequence from 1959 (ZR59) is the oldest known HIV-1 infection. Other historically documented sequences, important calibration points to convert evolutionary distance into time, are lacking, however; ZR59 is the only one sampled before 1976. Here we report the amplification and characterization of viral sequences from a Bouin's-fixed paraffin-embedded lymph node biopsy specimen obtained in 1960 from an adult female in Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the Congo (DRC)), and we use them to conduct the first comparative evolutionary genetic study of early pre-AIDS epidemic HIV-1 group M viruses. Phylogenetic analyses position this viral sequence (DRC60) closest to the ancestral node of subtype A (excluding A2). Relaxed molecular clock analyses incorporating DRC60 and ZR59 date the most recent common ancestor of the M group to near the beginning of the twentieth century. The sizeable genetic distance between DRC60 and ZR59 directly demonstrates that diversification of HIV-1 in west-central Africa occurred long before the recognized AIDS pandemic. The recovery of viral gene sequences from decades-old paraffin-embedded tissues opens the door to a detailed palaeovirological investigation of the evolutionary history of HIV-1 that is not accessible by other methods.

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Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960

Understanding the evolution of the human immunodeficiency virus (HIV) is crucial for reconstructing its origin, deciphering its interaction with the immune system and developing effective control strategies. Although it is clear that HIV-1 and HIV-2 originated in African primates, dating their transmission to humans is problematic, especially because of frequent recombination. Our ability to predict the spread of drug-resistance and immune-escape mutations depends on understanding how HIV evolution differs within and among hosts and on the role played by positive selection. For this purpose, extensive sampling of HIV genetic diversity is required, and is essential for informing the design of HIV vaccines.

/pdf/the-causes-and-consequences-of-hiv-evolution-3wexeizmnr.pdf

The causes and consequences of HIV evolution.

The purpose of this study was to document the genetic diversity of human immunodeficiency virus type 1 (HIV-1) in the Democratic Republic of Congo (DRC; formerly Zaire). A total of 247 HIV-1-positive samples, collected during an epidemiologic survey conducted in 1997 in three regions (Kinshasa [the capital], Bwamanda [in the north], and Mbuyi-Maya [in the south]), were genetically characterized in the env V3-V5 region. All known subtypes were found to cocirculate, and for 6% of the samples the subtype could not be identified. Subtype A is predominant, with prevalences decreasing from north to south (69% in the north, 53% in the capital city, and 46% in the south). Subtype C, D, G, and H prevalences range from 7 to 9%, whereas subtype F, J, K, and CRF01-AE strains represent 2 to 4% of the samples; only one subtype B strain was identified. The highest prevalence (25%) of subtype C was in the south, and CRF01-AE was seen mainly in the north. The high intersubtype variability among the V3-V5 sequences is the most probable reason for the low (45%) efficiency of subtype A-specific PCR and HMA (heteroduplex mobility assay). Eighteen (29%) of 62 samples had discordant subtype designations between env and gag. Sequence analysis of the entire envelope from 13 samples confirmed the high degree of diversity and complexity of HIV-1 strains in the DRC; 9 had a complex recombinant structure in gp160, involving fragments of known and unknown subtypes. Interestingly, the unknown fragments from the different strains did not cluster together. Overall, the high number of HIV-1 subtypes cocirculating, the high intrasubtype diversity, and the high numbers of possible recombinant viruses as well as different unclassified strains are all in agreement with an old and mature epidemic in the DRC, suggesting that this region is the epicenter of HIV-1 group M.

/pdf/unprecedented-degree-of-human-immunodeficiency-virus-type-1-4rvrsxkg4c.pdf

Unprecedented Degree of Human Immunodeficiency Virus Type 1 (HIV-1) Group M Genetic Diversity in the Democratic Republic of Congo Suggests that the HIV-1 Pandemic Originated in Central Africa

Methods: In February 1997, a large serosurvey was conducted on selected population groups from Kinshasa (capital city), Mbuji-May (southeast) and Bwamanda (northwest). Samples obtained from pregnant women, tuberculosis patients, commercial sex workers, blood donors and sexually transmitted disease patients were screened for the presence of HIV antibodies by a rapid assay and a commercial enzyme-linked immunosorbent assay. All reactive specimens were confirmed and discriminated by a line immunoassay, and were further tested for the presence of HIV-1 group O antibodies. Our results were compared to data reported in previous studies in Kinshasa. Results: Of a total 1970 samples collected, 21 9 (1 1 .I %) were HIV-I-reactive and seven (0.3%) were dually reactive to HIV-1 and HIV-2. No case of HIV-1 group O or HIV-2 infection was diagnosed. HIV seroprevalence in pregnant women was 3.1% (1 6 out of 51 I), 6.3% (1 9 out of 300) and 1.5% (one out of 65) in Kinshasa, MbujiMayi, and Bwamanda, respectively. HIV seroprevalence in tuberculosis patients was 26% (52 out of 200), 28% (1 7 out of 601, and 35.3% (29 out of 83), respectively. HIV seroprevalence among blood donors was 3.1% in Kinshasa and 2.8% in Mbuji-Mayi. Compared with data from previous studies performed in Kinshasa, no substantial change in HIV infection rates was observed among the selected population groups. Conclusions: Our results show that HIV prevalence rates have remained relatively unchanged in selected populations despite the political instability and poor environment observed since I991 in DRC. It also shows the presence, still at very low rate, of dual HIV-I/HIV-2 seropositivity and a growing problem of HIV infection in rural areas. In contrast to other Central African cou-ntries, no HIV-1 group O infections were detected in DRC.

/pdf/evidence-of-stable-hiv-seroprevalences-in-selected-pvotg79en1.pdf

Beni Bongo

Papers

Unprecedented Degree of Human Immunodeficiency Virus Type 1 (HIV-1) Group M Genetic Diversity in the Democratic Republic of Congo Suggests that the HIV-1 Pandemic Originated in Central Africa

Evidence of stable HIV seroprevalences in selected populations in the Democratic Republic of the Congo.