Pathogenesis of SIV pneumonia: Selective replication of viral genotypes in the lung

Tahar Babas, Elke Vieler, Debra A. Hauer, Robert John Adams, Patrick Tarwater, Kelly Fox, Janice E Clements, Mary Christine Zink

Research output: Contribution to journalArticle

Abstract

Lymphocytic interstitial pneumonia of HIV-infected individuals and SIV pneumonia of macaques are both characterized by diffuse infiltration of the lungs with lymphocytes, plasma cells, and macrophages. This study was undertaken to determine whether there are specific, macrophage-tropic genotypes that selectively replicate in the lung of macaques with SIV pneumonia, as in SIV encephalitis. Using a rapid, reproducible SIV/macaque model of AIDS, 11 pig-tailed macaques were intravenously inoculated with an immunosuppressive viral strain, SIV/DeltaB670, and a macrophage-tropic molecule clone, SIV/17E-Fr, and euthanized at 3 months postinoculation. All 11 macaques had severe (6 macaques) or moderate (5 macaques) pneumonia. To identify the viral genotypes that were replicating in the lung parenchyma, bronchoalveolar lavage (BAL) cells, and peripheral blood mononuclear cells (PBMC) of each macaque, RNA was isolated and the SIV env V1 region was amplified, cloned, and sequenced. Lung homogenates and BAL cells contained a more limited repertoire of viral genotypes than PBMC. SIV/17E-Fr was the major genotype in the lungs of 5 macaques and in BAL cells of 6 macaques. The remainder of the macaques had SIV/17E-Fr and the macrophage-tropic strains of SIV/DeltaB670 clones 2 and 12. In contrast, SIV/17E-Fr was the predominant strain in the PBMC of only 3 of 11 macaques The viral strain that predominated in PBMC was rarely the strain that predominated in the lungs (only 3 of 11 macaques). The severity of pulmonary lesions did not correlate with the levels of viral RNA in lung homogenates or in plasma. However, when only SIV/17E-Fr was expressed in the lung, the viral load in the lung was significantly higher (P = 0.016) than when SIV/DeltaB670 was present alone or in combination with SIV/17E-Fr. These data suggest that SIV pneumonia is associated with selective replication of specific macrophage-tropic genotypes in the lung and that SIV/17E-Fr has a selective advantage for replication in the lung.

Original languageEnglish (US)
Pages (from-to)371-381
Number of pages11
JournalVirology
Volume287
Issue number2
DOIs
StatePublished - Sep 1 2001

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Macaca
Pneumonia
Genotype
Lung
Bronchoalveolar Lavage
Macrophages
Blood Cells
Clone Cells
Interstitial Lung Diseases
Viral RNA
Encephalitis
Immunosuppressive Agents
Plasma Cells
Viral Load
Acquired Immunodeficiency Syndrome
Swine
HIV
Lymphocytes
RNA

Keywords

  • Envelope
  • Genotypes
  • HIV
  • LIP
  • Lung
  • Pneumonia
  • RT-PCR
  • SIV
  • Viral load

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Pathogenesis of SIV pneumonia : Selective replication of viral genotypes in the lung. / Babas, Tahar; Vieler, Elke; Hauer, Debra A.; Adams, Robert John; Tarwater, Patrick; Fox, Kelly; Clements, Janice E; Zink, Mary Christine.

In: Virology, Vol. 287, No. 2, 01.09.2001, p. 371-381.

Research output: Contribution to journalArticle

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