The genetic evolution of the envelope gene of simian immunodeficiency virus in cynomolgus macaques infected with a complex virus pool

Almond, Neil; Jenkins, Adrian; Ab, Heath; Taffs, L. F.; Kitchin, P.

doi:10.1016/0042-6822(92)90280-3

Cited by 15 publications

(9 citation statements)

References 22 publications

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“…The sole exception was the sequence variation observed in immunized macaque J174 across the V3 equivalent region of SIV gp120. In previous studies of the evolution ofgpl20 from SIVmac251-32H in vivo, this region has remained highly conserved (Almond et al, 1992b). It is of interest to note that on the day of challenge, this animal possessed detectable T cell proliferative responses to this region of the envelope protein (Jones et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Only 16 clones derived from the 11/88 virus challenge stock have been sequenced (Almond et al, 1992a). However, a 15 month longitudinal study of env sequences which appeared in vivo in two macaques inoculated with the 11/88 virus stock did not detect any sequences with an altered pattern of glycosylation across the V1 region of gpl20 (Almond et al, 1992b). It would seem, therefore, that many of the new sequences detected in this study arose from genetic change occurring to virus present in the initial infecting inoculum.…”

Section: Discussionmentioning

confidence: 99%

“…Following digestion with the restriction endonuclease SalI, the gpl20 region of the SIV env gene was amplified specifically, using two rounds of the PCR and nested oligonucleotide primer pairs, as described previously (Almond et al, 1992 b; the primers for the first round were SE6449N and SE8303C and for the second round were SE6574NSE and SE8127CKE). The number of cycles in each round of amplification was adjusted depending on whether the product was used directly for sequence analysis (40 cycles first round, 40 cycles second round), or else cloned into M13 mpl8 (10 cycles first round, 30 cycles second round) prior to sequencing (Almond et al, 1992b). Panels of recombinant clones o f gp 120 (Bg, 12 clones; B1, 12 clones; Bi, 11 clones; and Bm, 12 clones) were prepared from the product of the second round of amplification as described previously (Almond et al, 1992 a).…”

Section: Methodsmentioning

confidence: 99%

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Sequence Variation in the env Gene of Simian Immunodeficiency Virus Recovered from Immunized Macaques is Predominantly in the V1 Region

Almond¹,

Jenkins²,

Heath

et al. 1993

Journal of General Virology

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Three cynomolgus macaques were immunized with recombinant envelope protein preparations derived from simian immunodeficiency virus (SIV). Although humoral and cellular responses were elicited by the immunization regime, all macaques became infected upon challenge with 10 MIDs0 of the 11/88 virus challenge stock of SIVmac251-32H. The polymerase chain reaction was used to amplify proviral SIV gpl20 sequences present in the blood of both immunized and control macaques at 2 months post-infection. A comparison of the predominant sequences found in the region from V2 to V5 of gpl20 failed to differentiate provirus recovered from either immunized or control animals. A detailed investigation of sequences obtained from the hypervariable V1 region identified a mixture of sequences in both immunized and control macaques. Some sequences were identical to those previously detected in the virus challenge stock, whereas others had not been detected previously. Phenogram analysis of the new V1 sequences found in immunized animals revealed that they were quite distinct from those from the virus challenge stock and that they included alterations to potential N-linked glycosylation sites. In contrast, new sequence variants recovered from the control animals were closely related to sequences from the virus challenge stock. The difference in diversity of new V1 sequences recovered from immunized and control macaques was highly significant (P< 0.001). Thus, the presence of preexisting immune responses to SIV envelope protein is associated with greater genetic change in the V1 region of gpl20. These data are discussed in relation to the epitopes of SIV gpl20 that may confer protection from in vivo challenge.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Sequence Variation in the env Gene of Simian Immunodeficiency Virus Recovered from Immunized Macaques is Predominantly in the V1 Region

Almond¹,

Jenkins²,

Heath

et al. 1993

Journal of General Virology

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“…[1][2][3][4] This genetic variation is likely the consequence of error-prone reverse transcription and provides a large population pool that is continually shaped by selective forces in vivo. For example, a selective advantage might be conferred on a variant with the potential to escape host immune responses or to replicate more efficiently in a particular cell or tissue.…”

mentioning

confidence: 99%

Variation in Simian Immunodeficiency VirusenvV1 Region in Simian AIDS-Associated Lymphoma

Fortgang

Rege²,

Baskin³

et al. 2001

AIDS Research and Human Retroviruses

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Genetic variation of SIV env during the course of infection provides a large population pool that is continually shaped by selective forces in vivo and may influence the development of clinical disease. SAIDS-associated lymphoma (SAL) in the SIV-infected macaque is typically a clonal or oligoclonal mass of B cell origin, extranodal in anatomic distribution, in which SIV is restricted largely to infiltrating macrophages. To explore the degree of genetic variation in SIV env represented in SAL, a 480-bp DNA fragment containing the V1 region was PCR amplified from seven cases of SAL and from a nonneoplastic lymph node of an SIV-infected macaque. The nucleotide sequence of the V1 region was determined from at least 10 clones from multiple independent amplification reactions of each tissue. Overall, the degree of V1 variability within lymphomas was found not to be restricted but to resemble the heterogeneity reported in SIV-infected lymphoid and other tissues. V1 variation in the nonneoplastic lymph node was unexpectedly limited, perhaps related to the unusual disease condition associated with SAIDS in that animal. Unlike observations from SIV-infected tissues of animals without neoplastic disease, no increase was detected in the number of O- or N-linked glycosylation sites in the V1 regions isolated from lymphomas as compared with the original inoculum. These findings suggest that, within the microenvironment of the lymphoma, the immune evasion conferred by increased glycosylation may offer little selective advantage.

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“…3 The nef sequence used in clone GX2 was amplified from the peripheral blood mononuclear cells of macaque I227, 1 month after infection with the 11/88 stock of SIVmac 32H. 22 A 650-bp EcoRI-NdeI fragment of the nef clone X2 was used to replace the equivalent fragment of J5. The GX2 mutant is similar to J5 except for a deletion of amino acids 61-82 and three amino acid substitutions (tyrosine to serine at aa39, aspartate to glycine at aa47, and valine to isoleucine at aa117) in the Nef protein.…”

Section: Cell Lines and Virusesmentioning

confidence: 99%

Monoclonal Antibodies Recognize at Least Five Epitopes on the SIV Nef Protein and Identify an in Vitro-Induced Mutation

Arnold

Jenkins²,

Almond³

et al. 1999

AIDS Research and Human Retroviruses

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Eleven monoclonal antibodies (MAbs) to SIV Nef were produced and characterized. Five antibody-binding sites on SIV Nef were identified on the basis of the reactivity of the antibodies with recombinant proteins. Two of the five epitopes were defined using overlapping peptides. A further three epitopes could not be defined with peptides but all antibodies reacted in Western blot, suggesting that the epitopes were at least partially conformation dependent. Antibodies in two of the five epitope groups were further differentiated by competition analysis. The panel of MAbs described is able to distinguish between a number of recombinant Nef proteins currently under investigation in vivo in macaques. Two of the MAbs described are able to distinguish between the Nef protein from pathogenic (J5) and attenuated (C8) strains of SIV, thus providing useful tools for studying the relevance of the Nef protein in the pathogenesis of SIV infection. In FACScan analysis two of the MAbs, KK70 and KK75, were used to identify an in vitro-induced mutation in J5 Nef grown in C8166 cells. Sequence analysis of the phenotypic variants identified a mutation of the tryptophan (TGG) at amino acid 214 to a stop codon (TGA), thus truncating the Nef protein. The functional significance of this observation remains unclear but highlights the need to interpret data with caution if virus has been cultured in vitro even for a short period of time.

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The genetic evolution of the envelope gene of simian immunodeficiency virus in cynomolgus macaques infected with a complex virus pool

Cited by 15 publications

References 22 publications

Sequence Variation in the env Gene of Simian Immunodeficiency Virus Recovered from Immunized Macaques is Predominantly in the V1 Region

Sequence Variation in the env Gene of Simian Immunodeficiency Virus Recovered from Immunized Macaques is Predominantly in the V1 Region

Variation in Simian Immunodeficiency VirusenvV1 Region in Simian AIDS-Associated Lymphoma

Monoclonal Antibodies Recognize at Least Five Epitopes on the SIV Nef Protein and Identify an in Vitro-Induced Mutation

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