{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T01:31:56Z","timestamp":1792287116729,"version":"4.4.0"},"reference-count":101,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI083118"],"award-info":[{"award-number":["AI083118"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Primate lentiviruses, including the human and simian immunodeficiency viruses (HIV and SIV), produce infections marked by persistent, ongoing viral replication. This occurs despite the presence of virus-specific adaptive immune responses, including antibodies targeting the viral envelope glycoprotein (Env), and evolution of antibody-escape variants is a well-documented feature of lentiviral infection. Here, we examined the evolutionary dynamics of the SIV\n            <jats:italic>env<\/jats:italic>\n            gene during early infection (\u226429 weeks postinfection) in a cohort of four SIV\n            <jats:sub>mac<\/jats:sub>\n            251-infected rhesus macaques. We tracked\n            <jats:italic>env<\/jats:italic>\n            evolution during acute and early infection using frequent sampling and ultradeep sequencing of viral populations, capturing a transmission bottleneck and the subsequent reestablishment of Env diversity. A majority of changes in the gp120 subunit mapped to two short clusters, one in the first variable region (V1) and one in V4, while most changes in the gp41 subunit appeared in the cytoplasmic domain. Variation in V1 was dominated by short duplications and deletions of repetitive sequence, while variation in V4 was marked by short in-frame deletions and closely overlapping substitutions. The most common substitutions in both patches did not alter viral replicative fitness when tested using a highly sensitive, deep-sequencing-based competition assay. Our results, together with the observation that very similar or identical patterns of sequence evolution also occur in different macaque species infected with related but divergent strains of SIV, suggest that resistance to early, strain-specific anti-Env antibodies is the result of temporally and mutationally predictable pathways of escape that occur during the early stages of infection.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The envelope glycoprotein (Env) of primate lentiviruses mediates entry by binding to host cell receptors followed by fusion of the viral membrane with the cell membrane. The exposure of Env complexes on the surface of the virion results in targeting by antibodies, leading to selection for virus escape mutations. We used the SIV\/rhesus macaque model to track\n            <jats:italic>in vivo<\/jats:italic>\n            evolution of variation in Env during acute\/early infection in animals with and without antibody responses to Env, uncovering remarkable variation in animals with antibody responses within weeks of infection. Using a deep-sequencing-based fitness assay, we found substitutions associated with antibody escape had little to no effect on inherent replicative capacity. The ability to readily propagate advantageous changes that incur little to no replicative fitness costs may be a mechanism to maintain continuous replication under constant immune selection, allowing the virus to persist for months to years in the infected host.\n          <\/jats:p>","DOI":"10.1128\/jvi.01574-17","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T11:39:04Z","timestamp":1516189144000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["High-Resolution Sequencing of Viral Populations during Early Simian Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape from Emerging Env-Specific Antibody Responses"],"prefix":"10.1128","volume":"92","author":[{"given":"Sergio","family":"Ita","sequence":"first","affiliation":[{"name":"Virology Program, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison K.","family":"Hill","sequence":"additional","affiliation":[{"name":"Virology Program, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5556-2559","authenticated-orcid":false,"given":"Evan C.","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fay J.","family":"Dufort","sequence":"additional","affiliation":[{"name":"Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Viral Genomics Group, Broad Research Institute, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Newman","sequence":"additional","affiliation":[{"name":"Viral Genomics Group, Broad Research Institute, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivan","family":"Leviyang","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Georgetown University, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismael B.","family":"Fofana","sequence":"additional","affiliation":[{"name":"Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5991-5414","authenticated-orcid":false,"given":"Welkin E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Biology, Boston College, Chestnut Hill, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.53.082901.104053"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065x.2001.1830112.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/373123a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.8.5087-5094.1995"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/373117a0"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/35030124"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002721"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-205"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016048108"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-212"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000598"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05841-11"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0502-493"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/354453a0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1890"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000594"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00871-08"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02622-09"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.22.11623-11636.2002"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061383"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.12.7493-7500.1993"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01470"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00923-12"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06155-11"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0630530100"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.2174\/157016207782418515"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00239-07"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00201-06"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.4.1843-1854.1991"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.12.7025-7031.1991"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.9.5395-5402.1994"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-5-90"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.12.9475-9481.1997"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0348"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.1.209-217.1998"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.7.3561-3571.2004"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00107-12"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01382-08"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02741-09"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-3-19"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6822(03)00262-9"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01632-12"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.10.5937-5948.1992"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btx187"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03233-12"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01970-08"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.9.5721-5731.2005"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3617-3623.2006"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02265-08"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000365"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06682-11"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-7646(02)00123-1"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00017-07"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00335-13"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.10.009"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.11.009"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.02.011"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03327"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00201-13"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03507-12"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006620"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.10.6528-6531.2005"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.10.6523-6527.2005"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03235-14"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01871-10"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2075-2086.2002"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.10.7840-7845.1998"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.12.9808-9812.1997"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.1.375-381.2003"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.8.4557-4565.1993"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03608-14"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083182"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10373"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.012"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq152"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113425"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02544-12"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908492"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11519"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.06.022"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12053"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01893-12"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101176"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1093\/ve\/vex003"},{"key":"e_1_3_2_86_2","volume-title":"Guide for the care and use of laboratory animals","author":"National Research Council","year":"2011","unstructured":"National Research Council. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.","edition":"8"},{"key":"e_1_3_2_87_2","volume-title":"Public Health Service policy on humane care and use of laboratory animals","author":"Office of Laboratory Animal Welfare","year":"2015","unstructured":"Office of Laboratory Animal Welfare. 2015. Public Health Service policy on humane care and use of laboratory animals. Office of Laboratory Animal Welfare, National Institutes of Health, Washington, DC."},{"key":"e_1_3_2_88_2","volume-title":"Principles for the utilization and care of vertebrate animals used in testing, research and training","author":"Interagency Research Animal Committee","year":"1985","unstructured":"Interagency Research Animal Committee. 1985. Principles for the utilization and care of vertebrate animals used in testing, research and training. National Institutes of Health, Washington, DC."},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.10.7895-7902.1997"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8358-8367.2000"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00709-09"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.4.2855-2864.1998"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1896-1905.2002"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.8.6094-6099.1997"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.20.9388-9395.2000"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.19.12455-12463.2005"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2010.0029"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-475"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002529"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002417"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2011.05.010"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000272"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01574-17","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01574-17","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:44:50Z","timestamp":1646491490000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01574-17"}},"subtitle":[],"editor":[{"given":"Viviana","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":101,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1128\/JVI.01574-17"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01574-17","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]},"assertion":[{"value":"2017-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01574-17"}}