SIV vpx is essential for macrophage infection but not for development of AIDS.
Analysis of rhesus macaques infected with a vpx deletion mutant virus of simian immunodeficiency virus mac239 (SIVΔvpx) demonstrates that Vpx is essential for efficient monocyte/macrophage infection in vivo but is not necessary for development of AIDS. To compare myeloid-lineage cell infection in monkeys infected with SIVΔvpx compared to SIVmac239, we analyzed lymphoid and gastrointestinal tissues from SIVΔvpx-infected rhesus (n = 5), SIVmac239-infected rhesus with SIV encephalitis (7 SIV239E), those without encephalitis (4 SIV239noE), and other SIV mutant viruses with low viral loads (4 SIVΔnef, 2 SIVΔ3). SIV+ macrophages and the percentage of total SIV+ cells that were macrophages in spleen and lymph nodes were significantly lower in rhesus infected with SIVΔvpx (2.2%) compared to those infected with SIV239E (22.7%), SIV239noE (8.2%), and SIV mutant viruses (10.1%). In colon, SIVΔvpx monkeys had fewer SIV+ cells, no SIV+ macrophages, and lower percentage of SIV+ cells that were macrophages than the other 3 groups. Only 2 SIVΔvpx monkeys exhibited detectable virus in the colon. We demonstrate that Vpx is essential for efficient macrophage infection in vivo and that simian AIDS and death can occur in the absence of detectable macrophage infection.
Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, Massachusetts, United States of America.
Susan V
SV
Westmoreland
Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, Massachusetts, United States of America.
A Peter
AP
Converse
Case Western Reserve University School of Medicine, Department of Molecular Biology and Microbiology, Cleveland, Ohio, United States of America.
Kasia
K
Hrecka
Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, Massachusetts, United States of America.
Mollie
M
Hurley
Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, Massachusetts, United States of America.
Heather
H
Knight
AIDS and Cancer Virus Program NCI-Frederick, SAIC-Frederick, Frederick, Maryland, United States of America.
Michael
M
Piatak
AIDS and Cancer Virus Program NCI-Frederick, SAIC-Frederick, Frederick, Maryland, United States of America.
Jeffrey
J
Lifson
Harvard Medical School, New England Primate Research Center, Division of Comparative Pathology, Southborough, Massachusetts, United States of America.
Keith G
KG
Mansfield
Case Western Reserve University School of Medicine, Department of Molecular Biology and Microbiology, Cleveland, Ohio, United States of America.
Jacek
J
Skowronski
Harvard Medical School, New England Primate Research Center, Division of Microbiology, Southborough, Massachusetts, United States of America.
Ronald C
RC
Desrosiers
D000595:Amino Acid Sequence; D000818:Animals; D018792:Encephalitis, Viral / Q000401:mortality / Q000473:pathology / Q000821:virology*; D017353:Gene Deletion; D015870:Gene Expression; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008264:Macrophages / Q000473:pathology / Q000821:virology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000473:pathology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000401:mortality / Q000473:pathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity; D013154:Spleen / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D019562:Viral Load; D054334:Viral Regulatory and Accessory Proteins / Q000172:deficiency / Q000235:genetics*; D014779:Virus Replication
C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins