Natural Infection of Wild-Born Mandrills (Mandrillus sphinx) with Two Different Types of Simian Immunodeficiency Virus

Abstract

We found a novel primate lentivirus in mandrill (Mandrillus sphinx). To clarify the evolutionary relationships and transmission patterns of human/simian immunodeficiency virus (HIV/SIV), we screened blood samples from 30 wild-born healthy Cameroonian mandrills. Five (16.7%) of them were seropositive for SIV. Three SIV strains were isolated from the five seropositive mandrills by cocultivation of their peripheral blood mononuclear cells (PBMCs) with PBMCs of rhesus macaques, a human T cell line (M8166), and/or a cynomolgus macaque T cell line (HSC-F). One of the newly isolated SIV strains was intravenously inoculated into two rhesus macaques and resulted in chronic infection. In the SIV-infected macaques at 45 weeks after inoculation, we observed a mild decline in the number of peripheral CD4(+) lymphocytes, lymphadenopathy, and blastic follicular dendritic cells with mild follicular hyperplasia in the peripheral lymph nodes. A phylogenetic analysis based on the pol sequence showed that the newly found SIVs from Cameroonian mandrills did not cluster with SIVmndGB1, which is the former representative strain of SIVmnd. The SIVmnds from Cameroon formed a new, independent lineage that branched before the root of the HIV-1/SIVcpz lineage with 996 of 1000 bootstrap replications. They clustered host specifically, and exhibited about 16.9% diversity at the level of nucleotide sequence among Cameroonian SIVmnd strains. These results indicate that the SIVmnds isolated in Cameroon are a novel type of SIVmnd and have infected Cameroonian mandrills for a long time. We therefore designated the Cameroonian SIVmnd as SIVmnd type 2 and redesignated SIVmndGB1 as SIVmnd type 1. To date, M. sphinx is the only primate species other than humans that is naturally infected with two different types of SIV.

Immunovirological Analyses of Chronically Simian Immunodeficiency Virus SIVmnd-1- and SIVmnd-2-Infected Mandrills (Mandrillus sphinx)

“…Similar to the other viruses in this lineage, the genomic structure of SIVmnd-1 comprises only 5 accessory genes, with no vpu or vpx (64). Conversely, SIVmnd-2 is closely related to other Papionini-infecting SIVs (23,59,62), such as the viruses naturally infecting Mandrillus leucophaeus (SIVdrl) (9) and Cercocebus torquatus (SIVrcm) (6,15), and is a recombinant virus (3) harboring gag, pol, vif, vpx, vpr, rev, and tat sequences that are closely related to the sequences of those genes in SIVrcm, while its env and nef sequences are closely related to the env and nef sequences of SIVmnd-1 (59).…”

“…MNDs are endemic in Gabon and, to date, are the only natural host known to be infected with two types of SIV: SIVmnd type 1 (SIVmnd-1) and SIVmnd type 2 (SIVmnd-2) (23,59,62). Similar to HIV type 1 (HIV-1) and HIV-2, which have different structures and different origins resulting from cross-species transmissions of SIVcpz/gor from chimpanzees and gorillas (27,49,66) and SIVsmm from SMs (51), respectively, the two SIVmnd types also have different origins and structures (59).…”

Simian immunodeficiency virus types 1 and 2 (SIV mnd 1 and 2) have different pathogenic potentials in rhesus macaques upon experimental cross-species transmission

“…Mandrills (Mandrillus sphinx) are endemic in Gabon, central Africa, and are to date the only NHP species shown to be infected with two types of SIV: SIVmnd type 1 (SIVmnd-1) (Souquiere et al, 2001;Tsujimoto et al, 1988Tsujimoto et al, , 1989 and SIVmnd type 2 (SIVmnd-2) (Hu et al, 2003;Souquiere et al, 2001;Takehisa et al, 2001). These two SIVmnd types have different origins, with SIVmnd-1 belonging to the SIVlhoest lineage and clustering together with SIVlhoest from l'Hoesti monkeys and SIVsun from solatus monkeys (Beer et al, 1999;Hirsch et al, 1999;VandeWoude & Apetrei, 2006), and SIVmnd-2 being closer to other Papionini viruses, such as SIVdrl from drills (Mandrillus leuchophaeus) and SIVrcm (Hu et al, 2003;Souquiere et al, 2001;Takehisa et al, 2001).…”

“…These two SIVmnd types have different origins, with SIVmnd-1 belonging to the SIVlhoest lineage and clustering together with SIVlhoest from l'Hoesti monkeys and SIVsun from solatus monkeys (Beer et al, 1999;Hirsch et al, 1999;VandeWoude & Apetrei, 2006), and SIVmnd-2 being closer to other Papionini viruses, such as SIVdrl from drills (Mandrillus leuchophaeus) and SIVrcm (Hu et al, 2003;Souquiere et al, 2001;Takehisa et al, 2001). SIVmnd-2 is a recombinant virus, harbouring gag, pol, vif, vpx and tat sequences that are closely related to SIVrcm sequences, whereas its env and nef sequences are closely related to SIVmnd-1 (Hu et al, 2003;Souquière et al, 2001).…”

Characterization of a Novelvpu-Harboring Simian Immunodeficiency Virus from a Dent's Mona Monkey (Cercopithecus mona denti)

“…Primate lentiviruses for which full-length genome sequences are available have been classified, on the basis of phylogenetic analysis (6,16), into six approximately equidistant major groups or lineages, as follows: (i) SIVcpz from chimpanzees (Pan troglodytes) including also human immunodeficiency virus type 1 (HIV-1) (21, 31, 45, 56, 69; (ii) SIVsm from sooty mangabey (Cercocebus atys) together with HIV-2 (10,20,28); (iii) SIVagm from the four major species of African green monkeys, i.e., grivet (18), sabeus (33), vervet (26), and tantalus (60) (members of the genus Chlorocebus); (iv) SIVsyk from Sykes' monkeys (Cercopithecus mitis albogularis) (27) together with SIVmon from mona monkeys (Cercopithecus mona) (3,13), SIVgsn from greater spotnosed guenons (Cercopithecus nictitans) (16), SIVmus from mustached monkeys (Cercopithecus cephus) (13), and SIVdeb from De Brazza's monkeys (Cercopithecus neglectus) (6); (v) the SIVlhoest lineage, composed of SIVlhoest from L'Hoest monkeys (Cercopithecus lhoesti) (25), SIVsun from sun-tailed monkeys (Cercopithecus solatus) (4), and SIVmnd-1 from mandrills (Mandrillus sphinx) (68); and (vi) SIVcol from black and white colobus (Colobus guereza) (15). Several other viruses, notably SIVrcm from red-capped mangabeys (5), SIVmnd-2 from mandrills (61), and SIVdrl from drills (29) showed discordant phylogenetic clustering in different genomic regions, and are therefore considered recombinants (29,61,64). Partial sequences are available for SIVtal from talapoin monkeys (Miopithecus talapoin) (50) and for SIVschm from red-tailed guenon (Cercopithecus ascanius schmidti) (70); partial sequences from two species of western colobus are available: SIVwrc from western red colobus (Piliocolobus badius) and SIVolc from olive colobus (Procolobus verus) (14).…”