Rapid CD4+ T-lymphocyte depletion in rhesus monkeys infected with a simian-human immunodeficiency virus expressing the envelope glycoproteins of a primary dual-tropic Ethiopian Clade C HIV type 1 isolate.
Simian-human immunodeficiency virus (SHIV) chimerae with the envelope glycoproteins of X4 or R5/X4 HIV-1 isolates from clade B can cause rapid and severe CD4(+) T cell depletion and AIDS-like illness in infected monkeys. We created a SHIV (SHIV-MCGP1.3) expressing the envelope glycoproteins of a primary R5/X4, clade C HIV-1 isolate. Infection of a rhesus monkey with SHIV-MCGP1.3 resulted in a low level of viremia and no significant alteration in CD4(+) T-lymphocyte counts. However, serial intravenous passage of the virus resulted in the emergence of SHIV-MCGP1.3 variants that replicated efficiently and caused profound CD4(+) T cell depletion during the acute phase of infection. The CD4(+) T cell counts in the infected monkeys gradually returned to normal, and the animals remained healthy. The ability to cause rapid and profound loss of CD4(+) T lymphocytes in vivo is a property shared by passaged, CXCR4-using SHIVs, irrespective of the clade of origin of the HIV-1 envelope glycoproteins.
Department of Cancer Immunology/AIDS, Dana-Farber Cancer Institute, and Department of Pathology, Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mark
M
Cayabyab
Daniela
D
Rohne
Georgios
G
Pollakis
Claudia
C
Mische
Tseyanish
T
Messele
Almaz
A
Abebe
Bijan
B
Etemad-Moghadam
Peter
P
Yang
Scott
S
Henson
Michael
M
Axthelm
Jaap
J
Goudsmit
Norman L
NL
Letvin
Joseph
J
Sodroski
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D005002:Ethiopia; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D013997:Time Factors
D015686:Gene Products, env; D019713:Receptors, CCR5; D019718:Receptors, CXCR4