Physical location of host-range mutations of adenovirus type 5; deletion and marker-rescue mapping

Galos, Richard S.; Williams, Jim; Shenk, Thomas; Jones, Nicholas

doi:10.1016/0042-6822(80)90356-6

Cited by 39 publications

(19 citation statements)

References 13 publications

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“…However, some region lb mutants (e.g., hr7) may increase and others (e.g., d1313 and sub315) may decrease the level of expression of other adenovirus early regions (35). The hr6 and hr7 mutations map between 6.1 and 8.5 map units on the adenovirus genome, most probably within the intervening sequence of the 13S mRNA (11). This is the region bounded by the right ends of the deletions in sub316 and sub315.…”

Section: Resultsmentioning

confidence: 99%

Effect of deletions in adenovirus early region 1 genes upon replication of adeno-associated virus

Laughlin¹,

Jones²,

Carter³

1982

J Virol

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The growth of adeno-associated virus (AAV) is dependent upon helper functions provided by adenovirus. We investigated the role of adenovirus early gene region 1 in the AAV helper function by using six adenovirus type 5 (Ad5) host range mutants having deletions in early region 1. These mutants do not grow in human KB cells but are complemented by and grow in a line of adenovirus-transformed human embryonic kidney cells (293 cells); 293 cells contain and express the Ad5 early region 1 genes. Mutants having extensive deletions of adenovirus early region 1a (dl312) or regions 1a and 1b (dl313) helped AAV as efficiently as wild-type adenovirus in 293 cells, but neither mutant helped in KB cells. No AAV DNA, RNA, or protein synthesis was detected in KB cells in the presence of the mutant adenoviruses. Quantitative blotting experiments showed that at 20 h after infection with AAV and either dl312 or dl313 there was less than one AAV genome per cell. In KB cells infected with AAV alone, the unreplicated AAV genomes were detected readily. Apparently, infection with adenovirus mutant dl312 or dl313 results in degradation of most of the infecting AAV genomes. We suggest that at least an adenovirus region 1b product (and perhaps a region 1a product also) is required for AAV DNA replication. This putative region 1b function appears to protect AAV DNA from degradation by an adenovirus-induced DNase. We also tested additional Ad5 mutants (dl311, dl314, sub315, and sub316). All of these mutants were inefficient helpers, and they showed varying degrees of multiplicity leakiness. dl312 and dl313 complemented each other for the AAV helper function, and each was complemented by Ad5ts125 at the nonpermissive temperature. The defect in region 1 mutants for AAV helper function acts at a different stage of the AAV growth cycle than the defect in the region 2 mutant ts125.

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Section: Resultsmentioning

confidence: 99%

Effect of deletions in adenovirus early region 1 genes upon replication of adeno-associated virus

Laughlin¹,

Jones²,

Carter³

1982

J Virol

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“…Both viruses use the dL 327 14 backbone, contain E1/E3 deletions, and were generated as previously described. 7,15 Large-scale production of adenovirus and determination of viral titer was accomplished as described previously.…”

Section: Recombinant Adenovirusesmentioning

confidence: 99%

Adhesion of Monocytes to Vascular Cell Adhesion Molecule-1–Transduced Human Endothelial Cells

Gerszten

Lim

Ding

et al. 1998

Circulation Research

104

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Abstract-To study the role of vascular cell adhesion molecule-1 (VCAM-1) in monocyte recruitment and atherogenesis, we constructed a recombinant adenovirus, AdRSVrVCAM-1, carrying the rabbit VCAM-1 cDNA. We have previously shown that AdRSVrVCAM-1-transduced human umbilical vein endothelial cells (HUVECs) support the adhesion of CD4 ϩ CD45RO ϩ memory T lymphocytes under laminar flow conditions. We now demonstrate that AdRSVrVCAM-1-transduced HUVECs support the adhesion of peripheral blood monocytes at a shear stress of Յ1.5 dyne/cm 2 . Although VCAM-1 supported only firm adhesion of lymphocytes, it was able to mediate monocyte rolling, firm adhesion, and transmigration when expressed in the context of otherwise unactivated vascular endothelium. VCAM-1-transduced HUVECs supported the adhesion of as many as 4-fold more monocytes than T cells under laminar flow. The greater monocyte adhesion was explained at least in part by leukocyte-leukocyte interactions (secondary adhesions), which were not seen with T cells. These secondary monocyte interactions were specifically blocked by monoclonal antibodies to L-selectin and P-selectin glycoprotein ligand-1. These data demonstrate that VCAM-1 expressed in the context of unactivated vascular endothelium supports the adhesion of the leukocyte populations present in atherosclerotic plaque and may contribute to the predominance of monocytes over lymphocytes. (Circ Res. 1998;82:871-878.) Key Words: adenovirus Ⅲ adhesion Ⅲ atherosclerosis Ⅲ mononuclear leukocyte T he association between monocytes and atherosclerotic lesions, both in animal models and in humans, has long been recognized.1 Monocytes constitute Ϸ80% of the leukocytes in atherosclerotic plaque. Lymphocytes constitute 5% to 20% of this cell population and are predominantly CD4 ϩ CD45RO ϩ (memory) T cells. 2 Monocytes may contribute both to the development of atherosclerotic lesions and to events, such as acute plaque rupture, underlying acute coronary syndromes.3 VCAM-1 supports the adhesion of mononuclear leukocytes, including monocytes and lymphocytes, in simple in vitro assays. 4 It is expressed on the surface of endothelial cells during atherogenesis in animal models and is also detectable in human atherosclerotic lesions. 4,5 The expression of VCAM-1 in human atherosclerotic plaques appears to be correlated with increased accumulation of mononuclear cells.

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“…Recently, the lesion in the hr-i mutant was mapped between 1.3 and 3.7 units of the Ad5 genome by marker rescue (8). Berk et al.…”

mentioning

confidence: 99%

Control of adenovirus early gene expression: posttranscriptional control mediated by both viral and cellular gene products.

1981

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An adenovirus type 5 host range mutant (hr-i) located in region ElA and phenotypically defective in expressing viral messenger ribonucleic acid (RNA) from other early regions (Berk et al., Cell 17:935-944, 1979) was analyzed for accumulation of viral RNA in the presence of protein synthesis inhibitors. Nuclear RNA was transcribed from all early regions at the same rate, regardless of whether the drug was present or absent. As expected, low or undetectable levels of RNA were found in the cytoplasm of hr-l-infected cells compared with the wild-type adenovirus type 5 in the absence of drug. When anisomycin was added 30 min before hr-i infection, cytoplasmic RNA was abundant from early regions E3 and E4 when assayed by filter hybridization. In accordance, early regions E3and E4 viral messenger RNA species were detected by the Si endonuclease mapping technique only in hr-l-infected cells that were treated with the drug. Similar results were obtained by in vitro translation studies. Together, these results suggest that this adenovirus type 5 mutant lacks a viral gene product necessary for accumulation of viral messenger RNA, but not for transcription. It is proposed that a cellular gene product serves as a negative regulator of viral messenger RNA accumulation at the posttranscriptional level.

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Physical location of host-range mutations of adenovirus type 5; deletion and marker-rescue mapping

Cited by 39 publications

References 13 publications

Effect of deletions in adenovirus early region 1 genes upon replication of adeno-associated virus

Effect of deletions in adenovirus early region 1 genes upon replication of adeno-associated virus

Adhesion of Monocytes to Vascular Cell Adhesion Molecule-1–Transduced Human Endothelial Cells

Control of adenovirus early gene expression: posttranscriptional control mediated by both viral and cellular gene products.

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