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- All Subjects: LCMV
- Creators: Holechek, Susan
Description
Among wild rodent populations, vertical transmission is believed to constitute the primary route of infection for Lymphocytic Choriomeningitis Virus (LCMV), a non-lytic arenavirus with both acute and chronic forms. When carrier mice infected at birth with the acute Armstrong strain reproduce, they generate congenital carrier offspring containing a quasispecies of LCMV that includes Armstrong as well as its chronic Clone-13 variant. This study examined the genetic trends in the vertical transmission of LCMV from mothers infected perinatally with Clone-13. Viral isolates obtained from the serum of congenital carrier offspring were partially sequenced to reveal residue 260 in the glycoprotein-encoding region of their S segment, the site of a major amino acid change differentiating the chronic and acute strains. It was found that the phenylalanine-to-leucine mutation associated with Clone-13 was present in 100% of the isolates, strongly indicating that the offspring of Clone-13 carriers contain exclusively the chronic variant. This research has broad implications for the epidemiology of the virus, and, given the predominance of Armstrong in the wild, suggests that there must be a biological cost associated with Clone-13 infection in non-carriers.
ContributorsFrear, Cody Christian (Author) / Blattman, Joseph (Thesis director) / Hogue, Brenda (Committee member) / Holechek, Susan (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Pathogens such as lymphocytic choriomeningitis virus (LCMV) cause abnormalities in the nervous system of developing mice and humans. While humans are able to recover from infection and clear the virus, the mouse immune system tolerates the virus and lifelong infection ensues. In order to understand the factors driving LCMV evolution and evaluate its neuropathogenesis, a mouse model was needed. To establish congenital infection, newborn C57BL/6J mice were intra-cerebrally (i.c.) injected with 1 x 103 PFU LCMV Armstrong. Mice failed to thrive, resulting in a linear reduction in survival over the following two weeks and overall survival of 13%. Surviving mice did not have virus in their circulation after thirty days. As an alternative, 500 PFU of LCMV Armstrong was injected intraperitoneally (i.p.) into other litters. While this was associated with significantly reduced mortality, no mice in this group developed persistent infection either. ELISAs revealed that the mothers of injected pups developed a robust humoral response, confirming earlier reports that contact-associated acute infection occurs (Hotchin, 1971). In addition, the offspring of two litters of mice (out of six tested) also had antibodies to the virus, but at slightly lower titers. This indicates that the humoral response of the mothers may play a role in the neonatal clearance of infection. A higher titer of LCMV in i.p. injections may be necessary to overcome these barriers and establish chronic infection. In contrast, a lower dose of LCMV is recommended for i.c. injections, as the mortality seemed directly linked to the effects of the virus on offspring growth and development. Exposure to the virus in utero may also be necessary to increase survival and the likelihood of chronic infection.
ContributorsMorrow, Kristen Nicole (Author) / Blattman, Joseph (Thesis director) / Holechek, Susan (Committee member) / Franco, Lina (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05