Genetic mapping of lymphocytic choriomeningitis virus pathogenicity: virulence in guinea pigs is associated with the L RNA segment

Rivière, Yves; Ahmed, Rafi; Southern, Peter J.; Buchmeier, Michael J.; Oldstone, M B

doi:10.1128/jvi.55.3.704-709.1985

Cited by 82 publications

(42 citation statements)

References 16 publications

(10 reference statements)

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“…These strains also differ in their ability to cause a lethal disease in guinea pigs. Reassortant studies mapped pathogenic potential to the larger (L) of the two viral genomic RNA segments [31,50]. We have completed the nucleotide sequences for both the WE and ARM strains of LCMV and have found them to be 84% homologous (L RNA) [13,52].…”

Section: Discussionmentioning

confidence: 99%

LCMV-mediated hepatitis in rhesus macaques: WE but not ARM strain activates hepatocytes and induces liver regeneration

et al. 2004

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Lymphocytic chorimeningitis virus (LCMV), the prototype arenavirus, and Lassa virus (LASV), causative agent of Lassa hemorrhagic fever (LHF), belong to the Old World group of the family Arenaviridae. Both viruses have extensive strain diversity and significant variations in lethality and pathogenicity for man and experimental animals. We have shown that the LHF-like infection of rhesus macaques with the WE strain of LCMV affects liver functions, induces hepatocyte proliferation, and causes a rise in IL-6 and soluble TNF receptors (sTNFR) concomitant with a rise in viremia. The levels of IL-6 and sTNFR can serve as an additional diagnostic tool for liver involvement in pathogenesis of arenavirus infection. Mucosal inoculation of rhesus macaques with LCMV-WE can result in attenuated infection with a transient viremia and liver enzyme abnormalities. The ARM strain of LCMV shares 88% amino acid homology with WE. In contrast to LCMV-WE, ARM strain does not induce manifested disease in monkeys, does not affect liver functions, and does not induce hepatocyte proliferation. Previously we demonstrated that LCMV-ARM infection protected rhesus macaques challenged with LCMV-WE. Here we have shown that the protected animals have no signs of hepatitis and hepatocyte proliferation.

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Section: Discussionmentioning

confidence: 99%

LCMV-mediated hepatitis in rhesus macaques: WE but not ARM strain activates hepatocytes and induces liver regeneration

et al. 2004

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“…Virulence of viruses is determined by various aspects. The L RNA segment of lymphocytic choriomeningitis virus which encodes a viral RNA polymerase is important for viral replication and is associated with pathogenicity (Riviere, Ahmed, Southern, Buchmeier & Oldstone 1985). In the case of reovirus, the SI gene encodes the outer capsid protein, and determines differences in neurotropism and the different virulence patterns (Fields & Greene 1982).…”

Section: Discussionmentioning

confidence: 99%

Virulence of infectious pancreatic necrosis virus is associated with the larger RNA segment (RNA segment A)

Sano¹,

Okamoto²,

Fukuda³

et al. 1992

Journal of Fish Diseases

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Infectious pancreatic necrosis virus (IPNV) contains two segments of doublestranded RNA (the larger RNA segment. A; and a smaller RNA segment, B). The IPNVBuhl isolate belongs to the VR299 serotype, and eel virus European (EVE) is serologically the same as the Ab serotype. IPNV-Buhl is virulent to rainbow trout fry, Oneorhynchus mykiss (Walbaum), whereas EVE is avirulent. To determine the genetic basis for the difference of the virulence, intertypic reassortants were made between IPNV-Buhl and EVE. The reassortants with the genotypes of F/E (segment A of IPNV-Buhl and segment B of EVE) and E/P (segment A of EVE and segment B of IPNV-Buhl) were studied for their pathogenicity to rainbow trout fry. The P/E reassortant was highly virulent, similar to the IPNV-Buhl parent (P/P), while the E/P reassortant was avirulent, as was the EVE parent (E/E). A high level of viral replication was observed in almost all organs of the fry infected with the P/E reassortant and the IPNV-Buhl parent. In contrast, viral replication was restricted to the epidermal eells of the fry infected with the E/P reassortant and the EVE parent-The results demonstrate that the larger RNA segment (RNA segment A) of IPNV is related to eell tropism in vivo and is responsible for virulenee in rainbow trout fry.

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“…The S segment codes for the three major structural proteins : the internal nucleocapsid protein (NP ; 63 kD) and the two surface glycoproteins GP-1 (43 kD) and GP-2 (36 kD) that are derived from a common precursor polypeptide, GP-C. After coinfwtion of cells with two different LCMV strains, recombinants are generated by reassortment of genome segments. This permits genetic analysis of LCMV pathogenicity (9,13) .In this study, we have made reassortants between the parental Armstrong strain and the spleen variant clone 13 and examined their biological properties. Using this genetic approach in combination with complete sequence analysis of the S segment, we show that a single amino acid change in the viral glycoprotein profoundly affects the ability of LCMV to persist in adult mice.…”

mentioning

confidence: 99%

“…Identification of reassortant containing L segment of Armstrong spleen variant clone13 and S segment of parental wt Armstrong (svA/wtA genotype). Refer to…”

mentioning

confidence: 99%

Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice.

Matloubian¹,

Somasundaram²,

Kolhekar³

et al. 1990

The Journal of Experimental Medicine

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113

112

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SummaryThis study has identified a single amino acid change in the viral glycoprotein that profoundly affects the ability of lymphocytic choriomeningitis virus (LCMV) to persist in its natural host . Adult immunocompetent mice infected with a variant--of the Armstrong strain, spleen isolate clone 13 (svA/svA), harbor virus for several months and exhibit suppressed T cell responses . In contrast, adult mice infected with a reassortant virus (svA/wtA) that contains the L segment of the spleen variant and the S segment of the parental wt Armstrong, make potent LCMV specific CTL responses and clear the infection within 2-4 wk . These two viruses, spleen variant clone 13 and the reassortant svA/wtA, are identical in their noncoding regions and show no amino acid changes in any of their viral genes except for one substitution in the glycoprotein . The reassortant virus svA/wtA has a phenylalanine at amino acid residue 260 of the glycoprotein, whereas the spleen variant clone 13 has a leucine at this position . This study constitutes one of the first reports defining the genetic basis of viral persistence at the whole animal level, and identifying a single mutation that markedly increases the ability of a virus to persist in its natural host . S uccessful resolution of a viral infection depends upon a critical balance between the extent of viral spread and replication, and the magnitude of the host's immune response. We have been studying infection of mice with lymphocytic choriomeningitis virus (LCMV)t as a model system to understand the host and viral determinants that lead to viral clearance or persistence (1-4) . Infection of immunocompetent adult mice with the Armstrong strain of LCMV induces a potent antiviral T cellresponse and virus is eliminated within 2 wk . This clearance is mediated by CD8 * virus-specific cytotoxic T lymphocytes (4-7) . In contrast, infection of adult mice with a naturally selected isolate of Armstrong, spleen variant clone 13, results in a disseminated infection, with virus persisting for several months (1, 2). This chronic infection is associated with suppressed T cell responses and susceptibility to opportunistic infection (1, 2, 8) .The LCMV genome consists of two segments of singlestranded RNA, a large (L) segment of 7 .2 kb and a small (S) segment of 3 .4 kb (9-12) . The L RNA segment codes for a large protein, L (molecular mass 250 kD), that is be-1 Abbreviations used in this paper. L, large; LCMV, lymphocytic choriomeningitis virus; S, small; sv, spleen variants; wt, wild type.lieved to be the viral polymerase, and also contains a second open reading frame, designated Z, that encodes for a protein of "10-12 kD. The S segment codes for the three major structural proteins : the internal nucleocapsid protein (NP ; 63 kD) and the two surface glycoproteins GP-1 (43 kD) and GP-2 (36 kD) that are derived from a common precursor polypeptide, GP-C. After coinfwtion of cells with two different LCMV strains, recombinants are generated by reassortment of genome segments. This permits genetic a...

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Genetic mapping of lymphocytic choriomeningitis virus pathogenicity: virulence in guinea pigs is associated with the L RNA segment

Cited by 82 publications

References 16 publications

LCMV-mediated hepatitis in rhesus macaques: WE but not ARM strain activates hepatocytes and induces liver regeneration

LCMV-mediated hepatitis in rhesus macaques: WE but not ARM strain activates hepatocytes and induces liver regeneration

Virulence of infectious pancreatic necrosis virus is associated with the larger RNA segment (RNA segment A)

Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice.

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