Molecularly cloned simian immunodeficiency virus SIVagm3 is highly divergent from other SIVagm isolates and is biologically active in vitro and in vivo

Abstract

Simian immunodeficiency viruses have been isolated from African green monkeys originating from Ethiopia. A molecular clone, termed SIVagm3, was found to be highly divergent from SIVagmTYO-l in terms of its restriction map and partial nucleotide sequence. A premature stop codon present in the transmembrane protein of SIVagm TYO-l was absent in SIVagm3. SIVagm3 was biologically active in vitro and in vivo and displayed characteristics reminiscent of the wild-type virus. Biological activity was demonstrated by seroconversion of juvenile African green monkeys and Macaca nemestrina after inoculation. In contrast to antibody reactivity mainly directed against env proteins in naturally infected African green monkeys. African green monkeys and M. nemestrina infected with the cloned virus showed antibody reactivity directed against all major proteins as demonstrated by immunoblot analysis. The availability of a biologically fully competent molecular clone of SIVagm allows us now to address various pertinent questions in an animal model system which should help to understand features of human immunodeficiency virus infection in human beings.

Neutralizing antibody responses in Africa green monkeys naturally infected with simian immunodeficiency virus (SIVagm)

“…The choice of target cells used to detect those neutralizing antibodies was critical, where little or no neutralization of SIVagm1532 was detected in Molt-4 clone 8 cells. Based on this latter observation, the inability to detect a strong neutralizing antibody response in an earlier study of SIV-infected African green monkeys [3 51 may have been due to the fact that neutralization was measured in Molt-4 clone 8 cells. The choice of cells used for assay has been shown to have a minor influence on the detection of neutralizing antibodies to HIV-1 [32] and primary SIVmac251 [25], but not nearly to the same extent as that seen here.…”

“…SIVagm has a similar genomic organization to HIV-1 and HIV-2 and is genetically equidistant to both types of HIV [3,41. The host range for established cell lines is similar to HIV, although minor differences have been observed [23, 351. SIVagm exhibits extensive genetic variation that might even surpass that seen for HIV-1 [3,4,21,261.…”

“…SIVagm has a similar genomic organization to HIV-1 and HIV-2 and is genetically equidistant to both types of HIV [3,41. The host range for established cell lines is similar to HIV, although minor differences have been observed [23, 351. SIVagm exhibits extensive genetic variation that might even surpass that seen for HIV-1 [3,4,21,261. The amount of virus detected in the cells and plasma of SIV-infected African green monkeys is similar to that seen in HIV-1-infected, asymptomatic humans, although it does not appear to rise to levels seen in later stages of HIV-1 infection [18].…”

Simian Immunodeficiency Virus (SIV) from Sun-Tailed Monkeys (Cercopithecus solatus): Evidence for Host-Dependent Evolution of SIV within theC. lhoestiSuperspecies

“…At present these primate lentiviruses can be classified into five lineages based upon the sequence and functional similarity of their genes (31,62). These five lineages are represented by (i) SIVcpz from chimpanzees (Pan troglodytes) together with HIV-1 (19,34,35,54,68), (ii) SIVsm from sooty mangabeys (Cercocebus torquatus atys) together with HIV-2 (10,33,46,55,58), (iii) SIVagm from four species of African green monkeys (members of the Chlorocebus aethiops superspecies) (4,6,12,16,32,36,38,47), (iv) SIVsyk from Sykes' monkeys (Cercopithecus mitis albogularis) (13,30), and (v) SIVmnd from a mandrill (Mandrillus sphinx) together with SIVlhoest from l'hoest monkeys (Cercopithecus lhoesti lhoesti) (28,66,67).…”

Induction of AIDS by simian immunodeficiency virus from an African green monkey: species-specific variation in pathogenicity correlates with the extent of in vivo replication

“…Isolates from other SIV groups have not been characterized as extensively in terms of pathogenesis, and it has been generally assumed that SIVmnd, SIVagm, and SIVsyk are nonpathogenic both for their natural host and in experimentally inoculated macaques. For example, experimental inoculation of cynomolgus or rhesus macaques with SIVagm strains results in persistent infection with a characteristically low virus load and no associated disease (1,4,22,24). A similar finding was observed for ma-caques inoculated with SIVsyk (20).…”