Characterization of a novel simian immunodeficiency virus from guereza colobus monkeys (Colobus guereza) in Cameroon: a new lineage in the nonhuman primate lentivirus family

Abstract

Exploration of the diversity among primate lentiviruses is necessary to elucidate the origins and evolution of immunodeficiency viruses. During a serological survey in Cameroon, we screened 25 wild-born guereza colobus monkeys (Colobus guereza) and identified 7 with HIV/SIV cross-reactive antibodies. In this study, we describe a novel lentivirus, named SIVcol, prevalent in guereza colobus monkeys. Genetic analysis revealed that SIVcol was very distinct from all other known SIV/HIV isolates, with average amino acid identities of 40% for Gag, 50% for Pol, 28% for Env, and around 25% for proteins encoded by five other genes. Phylogenetic analyses confirmed that SIVcol is genetically distinct from other previously characterized primate lentiviruses and clusters independently, forming a novel lineage, the sixth in the current classification. Cercopithecidae monkeys (Old World monkeys) are subdivided into two subfamilies, the Colobinae and the Cercopithecinae, and, so far, all Cercopithecidae monkeys from which lentiviruses have been isolated belong to the Cercopithecinae subfamily. Therefore, SIVcol from guereza colobus monkeys (C. guereza) is the first primate lentivirus identified in the Colobinae subfamily and the divergence of SIVcol may reflect divergence of the host lineage.

FIG. 1

Antibody profiles of guereza colobus monkeys (Colobus guereza) on a commercial line-immunoassay, Innolia HIV-1/HIV-2 (Innogenetics). The correspondence of the different bands observed are indicated on the left of the positive control strip. The numbers 163, 216, 243, 246, and 247 were assigned to five different colobus monkeys, from whom whole-blood samples were collected.

FIG. 2

(A) Genomic organization of SIVcol from guereza colobus monkeys; (B) sequence of the SIVcol LTR. The U3, R, and U5 regions are indicated. The NF-κB and SP-1 sites, the TATA box, the poly(A) signal, and the primer binding site (PBS) are noted with a line above the sequence. The TAR region is shown by a dashed line below the sequence.

FIG. 3

Alignment of gp120 of SIVcol and an SIV representative of each of the five other lineages. The amino acid sequence of SIVcol is shown on the top line, with variable regions (V1 to V5) analogous to those observed in other SIVs indicated. The CD4 binding domain is shown. An asterisk represents a conserved cysteine residue. Potential N-linked glycosylation sites are noted with a line above. Dots indicate amino acid identity at a residue, and dashes indicate gaps introduced to optimize alignment.

FIG. 4

Diversity plot comparing SIVcol with representatives of the five major lineages of primate lentiviruses, i.e., SIVcpz, SIVmnd, SIVsyk, SIVsm, and SIVagm. Protein sequence difference is plotted for windows of 200 amino acids, moved in steps of 20.

FIG. 5

Phylogenetic relationship of SIVcol to other primate lentiviruses. This tree was derived by neighbor-joining analysis from a concatenated Gag-Pol-Vif-Env-Nef protein alignment. The reliability was estimated by 1,000 bootstrap replicates; only values above 75% are shown. Branch lengths are drawn to scale. Bar, 0.1 amino acid replacement per site.

FIG. 6

Phylogenetic tree showing the relationships of the 3 SIVcol pol sequences (650 bp) to equivalent sequences from selected HIV/SIV group viruses representing the five different lineages. Sites at which there was a gap in any of the aligned sequences were not used to calculate distances. Phylogenetic relationships were computed from these distances by the neighbor-joining method. The significance of the branching order was estimated by the bootstrap method (1,000 resampling).