David Robertson, Véronique Lemée, Fabienne De Oliveira, Florence Damond, François Simon, Philippe Mauclère, Marie Leoz, Jean-Christophe Plantier, Felix Feyertag, Guillaume Lachenal, Anfumbom Kfutwah, Laboratoire de virologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Faculty of Life Sciences [Manchester], University of Manchester [Manchester], Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Sciences, Philosophie, Histoire (SPHERE UMR 7219), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Laboratoire de Virologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and This work was supported by the Institut de Veille Sanitaire, the Universitary Hospital of Rouen, the University of Rouen and the Centre Pasteur du Cameroun. FF is funded by a BBSRC studentship to DLR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Unlike the pandemic form of HIV-1 (group M), group O viruses are endemic in west central Africa, especially in Cameroon. However, little is known about group O’s genetic evolution, and why this highly divergent lineage has not become pandemic. Using a unique and large set of group O sequences from samples collected from 1987 to 2012, we find that this lineage has evolved in successive slow and fast phases of diversification, with a most recent common ancestor estimated to have existed around 1930 (1914–1944). The most rapid periods of diversification occurred in the 1950s and in the 1980s, and could be linked to favourable epidemiological contexts in Cameroon. Group O genetic diversity reflects this two-phase evolution, with two distinct populations potentially having different viral properties. The currently predominant viral population emerged in the 1980s, from an ancient population which had first developed in the 1950s, and is characterized by higher growth and evolutionary rates, and the natural presence of the Y181C resistance mutation, thought to confer a phenotypic advantage. Our findings show that although this evolutionary pattern is specific to HIV-1 group O, it paralleled the early spread of HIV-1 group M in the Democratic Republic of Congo. Both viral lineages are likely to have benefited from similar epidemiological contexts. The relative role of virological and social factors in the distinct epidemic histories of HIV-1 group O and M needs to be reassessed., Author Summary HIV-1 group O is one of the causal agents of AIDS, together with HIV-1 groups M (responsible for the pandemic), N and P (15 and 2 cases detected respectively, from Cameroon) and HIV-2 groups A to I (mostly found in West Africa), each group resulting from a distinct cross species transmission event from non-human primates. Even though mostly restricted to Cameroon, group O infections have been found in other African countries as well as in Europe and in the US. Due to their genetic distance from the pandemic HIV-1 group M, group O viruses still impact diagnosis, virological and therapeutic monitoring. Moreover, very few data are available on the natural history and epidemiology of these infections, as well as their genetic diversity and evolution. In particular, there is currently no explanation of the lack of spread of these variants, compared to the pandemic viruses from group M. Analysis of HIV-1 group O molecular evolution, from sequences spanning more than 2 decades, is an opportunity to better understand the phylodynamics of group O infection. We investigate it further by producing the largest set of group O sequences described. We show that the previous classifications proposed do not agree with each other and do not fit with the extensive genetic diversity of this group. We also estimate that group O MRCA existed in the 1930s (95% Higher Posterior Density: 1914–1944), and show that group O has diversified during two successive phases that could be linked to the specific historical context of Cameroon. These results contribute to a better understanding of the factors influencing HIV evolution, especially in the local context of west central Africa and lead to new hypotheses on the limited diffusion of such variants.