Neutralization sensitivity of a simian-human immunodeficiency virus (SHIV-HXBc2P 3.2N) isolated from an infected rhesus macaque with neurological disease.
Simian-human immunodeficiency virus (SHIV) chimerae, after in vivo passage in monkeys, can induce acquired immunodeficiency syndrome (AIDS)-like illness and death. A monkey infected with the molecularly cloned, pathogenic SHIV-HXBc2P 3.2 exhibited multifocal granulomatous pneumonia as well as progressive neurological impairment characterized by tremors and pelvic limb weakness. SHIV-HXBc2P 3.2N was isolated from brain tissue explants and characterized. Viruses with the envelope glycoproteins of SHIV-HXBc2P 3.2N exhibited increased sensitivity to soluble CD4 and several neutralizing antibodies compared with viruses with the parental SHIV-HXBc2P 3.2 envelope glycoproteins. By contrast, viruses with SHIV-HXBc2P 3.2 and SHIV-HXBc2P 3.2N envelope glycoproteins were neutralized equivalently by 2G12 and 2F5 antibodies, which are rarely elicited in HIV-1-infected humans. A constellation of changes involving both gp120 and gp41 envelope glycoproteins was responsible for the difference in susceptibility to neutralization by most antibodies. Surprisingly, the gain of an N-linked glycosylation site in the gp41 ectodomain contributed greatly to neutralization sensitivity. Thus, the environment of the central nervous system, particularly in the context of immunodeficiency, allows the evolution of immunodeficiency viruses with greater susceptibility to neutralization by antibodies.
Song
Byeongwoon
B
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Cayabyab
Mark
M
Phan
Ngoc
N
Wang
Liping
L
Axthelm
Michael K
MK
Letvin
Norman L
NL
Sodroski
Joseph G
JG
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000821:virology; D015704:CD4 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000821:virology*; D009500:Neutralization Tests; D016865:Reassortant Viruses / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
D015704:CD4 Antigens; D006023:Glycoproteins; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41