Non-M variants of human immunodeficiency virus type 1

Abstract

The AIDS pandemic that started in the early 1980s is due to human immunodeficiency virus type 1 (HIV-1) group M (HIV-M), but apart from this major group, many divergent variants have been described (HIV-1 groups N, O, and P and HIV-2). The four HIV-1 groups arose from independent cross-species transmission of the simian immunodeficiency viruses (SIVs) SIVcpz, infecting chimpanzees, and SIVgor, infecting gorillas. This, together with human adaptation, accounts for their genomic, phylogenetic, and virological specificities. Nevertheless, the natural course of non-M HIV infection seems similar to that of HIV-M. The virological monitoring of infected patients is now possible with commercial kits, but their therapeutic management remains complex. All non-M variants were principally described for patients linked to Cameroon, where HIV-O accounts for 1% of all HIV infections; only 15 cases of HIV-N infection and 2 HIV-P infections have been reported. Despite improvements in our knowledge, many fascinating questions remain concerning the origin, genetic evolution, and slow spread of these variants. Other variants may already exist or may arise in the future, calling for close surveillance. This review provides a comprehensive, up-to-date summary of the current knowledge on these pathogens, including the historical background of their discovery; the latest advances in the comprehension of their origin and spread; and clinical, therapeutic, and laboratory aspects that may be useful for the management and the treatment of patients infected with these divergent viruses.

Fig 1

Phylogenetic relationships between the HIV-1, SIVcpz, and SIVgor lineages. (Reprinted from reference with permission of the publisher.)

Fig 2

Scenarios for transmission of SIV from chimpanzees and gorillas to humans, explaining the emergence of HIV-O and HIV-P. Empty circles, SIV transmission events from chimpanzees; solid circles, SIV transmission events from gorillas. (A) SIVcpz transmitted to gorillas on one occasion, followed by transmission of SIVgor to humans on two occasions (groups O and P). (B) SIVcpz transmitted to humans on one occasion (group O) and to gorillas on one occasion and then transmission of SIVgor to humans on one occasion (group P). (Modified from reference with permission of the publisher.)

Fig 3

Adaptive evolution of the Nef and Vpu viral proteins in primate lentiviruses. The degradation of CD4 receptors by the Nef and Vpu viral proteins and their antagonistic activity against the restriction factor tetherin are represented by +, and the absence of these properties or very low activity is represented by −. The Nef proteins of SIVcpz and SIVgor degrade CD4 receptors and antagonize the factor tetherin in their respective hosts, whereas those of HIV-1 do not have any activity against human tetherin. Only the Vpu protein from HIV-1 group M, through adaptive evolution, possesses antitetherin properties and degrades CD4 receptors. (Reprinted from reference with permission from Elsevier.)

Fig 4

Comparison of phylogenetic trees constructed from 117 HIV-O sequences (a) and 55 HIV-M sequences (b) in the integrase region (603 bp). ACC, GenBank accession number. (Modified from reference with permission of the publisher.)

Fig 4

Comparison of phylogenetic trees constructed from 117 HIV-O sequences (a) and 55 HIV-M sequences (b) in the integrase region (603 bp). ACC, GenBank accession number. (Modified from reference with permission of the publisher.)

Fig 5

Molecular epidemiology of HIV-1 non-M variants. Shown is a representation of the worldwide distribution of HIV-1 non-M variants according to the number of reported cases published. Three maps are presented for the HIV-O, HIV-N, and HIV-P variants. Only Europe and Africa are represented for the distribution of the variants N and P, as no infection was reported outside these regions. ∗, Togo is the most likely place of contamination of the HIV-N case reported by Delaugerre et al. (28), but no case was reported from this country.

Fig 6

Western blot profiles of HIV-1 groups M, N, O, and P. The figure shows examples of Western blot reactivities with sera positive for the four groups. The group P-positive sample comes from the patient infected by the prototype strain RBF168. Of note, the group N-positive serum does not present a complete profile, due to advanced-stage disease (see reference for complete profiles). The molecular masses of HIV-1 glycoproteins (gp) and proteins (p) are indicated in kDa.