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

Almond, Neil; Jenkins, Adrian; Heath, Alan; Kitchin, P.

doi:10.1099/0022-1317-74-5-865

Cited by 27 publications

(24 citation statements)

References 16 publications

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“…Our examination revealed the V1 and V2 regions of SIVsmE660 were not conserved as like the V3 region. These findings are also consistent with other reports describing sequence variation mostly in the V1 region of SIV infections [47,48]. Therefore, the V1 and V2 regions in the envelope glycoprotein may carry the potentiality in determining receptor tropism.…”

Section: Discussionsupporting

confidence: 92%

CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for limited human and simian immunodeficiency viruses

et al. 2014

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BackgroundThe chemokine receptors (CKRs), mainly CCR5 and CXCR4 function as major coreceptors in infections caused by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Approximately 20 G protein-coupled receptors (GPCRs) have been identified as minor coreceptors, alike CCR6 that we reported recently. Since CKR-L3 is indentified as a natural isoform of CCR6, we attempted in this study to explore the coreceptor function of CKR-L3.MethodsNP-2 cells transduced with CD4-receptor (NP-2/CD4) normally remain resistant to HIV or SIV infection. However, the introduction of functional coreceptors can make these cells susceptible to these viruses. NP-2/CD4/CKR-L3 cells were produced to examine the coreceptor activity of CKR-L3. Likely, CCR6-isoform and the major coreceptors, CCR5 and CXCR4 were also examined in parallel. Presence of viral antigen in infected NP-2/CD4/coreceptor cells was detected by indirect immunofluorescence assay (IFA). The results were validated by detection of syncytia, proviral DNA and by measuring reverse transcriptase (RT) activities.ResultsHIV-2MIR and SIVsmE660 were found to infect NP-2/CD4/CKR-L3 cells, indicative of the coreceptor function of CKR-L3. Viral antigens appeared faster in NP-2/CD4/CKR-L3 cells than in NP-2/CD4/CCR6, indicating that CKR-L3 is a more efficient coreceptor. Moreover, syncytia formation was more rapid and RT release evidenced earlier and at higher levels with CKR-L3 than with CCR6. Sequence analysis in the C2-V3 envelope region of HIV-2MIR replicated through CKR-L3 and CCR6 coreceptor showed two and three amino acid substitutions respectively, in the C2 region compared to the CCR5-variant. The SIVsmE660-CKRL3 variant showed three amino acid substitutions in the V1 region, one change in the V2 and two changes in the C2 region. The SIVsmE660-CCR6 variant produced two changes in the V1 region, and three in the C2 region.ConclusionsIsoform CKR-L3 exhibited coreceptor activity for limited primary HIV and SIV isolates with better efficiency than the parent CCR6-isoform. Amino acid substitutions in the envelope region of these viruses may confer selective pressure towards CKR-L3-use. CKR-L3 with other minor coreceptors may contribute to HIV and SIV pathogenesis including dissemination, trafficking and latency especially when major coreceptors become compromised. However, further works will be required to determine its clinical significance in HIV and SIV infection.

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Section: Discussionsupporting

confidence: 92%

CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for limited human and simian immunodeficiency viruses

et al. 2014

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“…8 The most extensive variation in the SIV genome has been localized to the gene encoding the surface envelope glycoprotein, gp120, specifically to the hypervariable region V1. 1,2,9,10 Data indicate that the V1 region encodes a principal neutralizing determinant for SIV 7 ; thus V1 variation during the course of infection might provide a selective advantage in immune evasion. V1 variation also apparently confers differential replicative potential, as indicated in a study of the individual members of the quasispecies in vivo.…”

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confidence: 97%

“…We chose to examine the V1 region so that our results could be compared with related studies, 4,12,20 and because V1 has been shown to be the most variable region of SIV gp120. 1,2,9,10 We examined DNA from lymphomas of six SIV-infected rhesus macaques, from one SIV-infected cynomolgus macaque, and from the lymph node of an SIV-infected macaque that did not develop lymphoma ( Table 1). Each of these animals was infected with a genetically complex SIV stock, generally SIV/DeltaB670.…”

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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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“…Because these regions were defined for animals with robust immune responses, particularly neutralizing antibody responses, evolution of these regions is likely to be the result of viral mechanisms of immune evasion. The primary regions subject to genetic variation during the course of SIV infection in macaques are limited to the V1 and V4 regions of the envelope glycoprotein (3,20,55). Variation in the V1 region is characterized by substitutions and short, in-frame deletions and insertions.…”

mentioning

confidence: 99%

Unique Pattern of Convergent Envelope Evolution in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques: Association with CD4-Independent Usage of CCR5

Dehghani

Puffer

Doms

et al. 2003

J Virol

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The rate of disease development in simian immunodeficiency virus (SIV) infection of macaques varies considerably among individual macaques. While the majority of macaques inoculated with pathogenic SIV develop AIDS within a period of 1 to 2 years, a minority exhibit a rapid disease course characterized by absence or transience of humoral and cellular immune responses and high levels of virus replication with widespread dissemination of SIV in macrophages and multinucleated giant cells. The goal of this study was to examine viral evolution in three SIVsmE543-3-inoculated rapid progressors to determine the contribution of viral evolution to the development of rapid disease and the effect of the absence of immune pressure upon viral evolution. PCR was used to amplify and clone the entire SIV genome from tissues collected at necropsy, and the course of viral evolution was assessed by env sequences cloned from sequential plasma samples of one rapid progressor (RP) macaque. The majority of sequence changes in RP macaques occurred in the envelope gene. Substitutions were observed in all three animals at specific conserved residues in envelope, including loss of a glycosylation site in V1/V2, a D-to-N/V substitution in a highly conserved GDPE motif, and a P-to-V/H/T substitution in the V3 loop analog. A cell-cell fusion assay revealed that representative env clones utilized CCR5 as a coreceptor, independent of CD4. The selection of specific substitutions in envelope in RP macaques suggests novel selection pressures on virus in such animals and suggests that viral variants that evolve in these animals may play a role in disease progression.

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

Cited by 27 publications

References 16 publications

CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for limited human and simian immunodeficiency viruses

CKR-L3, a deletion version CCR6-isoform shows coreceptor-activity for limited human and simian immunodeficiency viruses

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

Unique Pattern of Convergent Envelope Evolution in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques: Association with CD4-Independent Usage of CCR5

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