Principles of Virology, Volume 2. S. Jane Flint

pathogens: insights from Ebola virus. Nat Immunol 8:1159–1164.

       Papers of Special Interest

      Ida-Hosonuma M, Iwasaki T, Yoshikawa T, Nagata N, Sato Y, Sata T, Yoneyama M, Fujita T,Taya C, Yonekawa H, Koike S. 2005. The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus. J Virol 79:4460–4469.

       Results from this paper show that the alpha/beta interferon system plays an important role in determining tissue tropism by protecting nontarget tissues that are potentially susceptible to infection.

      Maidji E, Genbacev O, Chang HT, Pereira L. 2007. Developmental regulation of human cytomegalovirus receptors in cytotrophoblasts correlates with distinct replication sites in the placenta. J Virol 81:4701–4712.

       This paper shows that virus interactions with cytotrophoblasts expressing receptors in the placenta are impacted differentially during development and correlate with spatially distinct sites of viral replication in maternal and fetal compartments.

      Publicover J, Ramsburg E, Robek M, Rose JK. 2006. Rapid pathogenesis induced by a vesicular stomatitis virus matrix protein mutant: viral pathogenesis is linked to induction of tumor necrosis factor alpha. J Virol 80:7028–7036.

       Using viral mutants and knockoutmice, the authors show the role of tumor necrosis factor alpha in the pathogenesis of vesicular stomatitis virus.

      Rambaut A, Pybus OG, Nelson MI, Viboud C, Taubenberger JK, Holmes EC. 2008. The genomic and epidemiological dynamics of human influenza A virus. Nature 453:615–619.

       The conclusions from this viral ecology paper show that new influenza lineages are seeded from a persistent reservoir, which they hypothesize is located in the tropics.

      Rivers TM. 1937. Viruses and Koch’s postulates. J Bacteriol 33:1–12.

       This paper is a classic treatise on the application and challenges of Koch’s postulates to viral infections.

      Sacher T, Podlech J, Mohr CA, Jordan S, Ruzsics Z, Reddehase MJ, Koszinowski UH. 2008. The major virus-producing cell type during murine cytomegalovirus infection, the hepatocyte, is not the source of virus dissemination in the host. Cell Host Microbe 3:263–272.

       In evaluating viral production and spread, these authors found that the cell type producing the most viruses was not necessarily the one responsible for virus dissemination within the host.

      Smith GA, Pomeranz L, Gross SP, Enquist LW. 2004. Local modulation of plus-end transport targets herpesvirus entry and egress in sensory axons. Proc Natl Acad Sci U S A 101:16034–16039.

       In examining herpes virus transport in neurons, Enquist and colleagues show that transport direction is not modulated globally by viral gene expression, but rather directly by a component of the viral particle.

      Tyler KL, McPhee DA, Fields BN. 1986. Distinct pathways of viral spread in the host determined by reovirus S1 gene segment. Science 233:770–774.

       With the use of reassortant viruses, the reoviral S1 RNA segment was shown to be responsible for determining the capacity of reoviruses to spread to the central nervous system (CNS).

      Tyler KL, Virgin HW IV, Bassel-Duby R, Fields BN. 1989. Antibody inhibits defined stages in the pathogenesis of reovirus serotype 3 infection of the central nervous system. J Exp Med 170:887–900.

       The authors conclude that systemic immunoglobulin G does not play a significant role at the primary site of infection with reoviruses, whereas it acts to prevent infection of the CNS and extension of infection within the CNS.

      Wallace GD, Buller RM. 1985. Kinetics of ectromelia virus (mousepox) transmission and clinical response in C57BL/6j, BALB/cByj and AKR/J in bred mice. Lab Anim Sci 35:41–46.

       Differences in infection kinetics were chronicled in various inbred mouse strains, identifying key host restriction factors that limit viral infection or disease.

STUDY QUESTIONS

      1 Which of the following can impact the ability of a barrier to prevent infection of an individual host? (Select all that are appropriate.)Time of year and humidityGenetics of the potential hostConcentration of the viral inoculumHealth of the host

      2 Not all virus encounters with receptor-bearing cells lead to a productive infection. List four obstacles that could preclude a productive infection.

      3 What host and viral parameters govern whether a virus will remain localized or can disseminate into other tissues?

      4 Define three ways by which viruses can gain access to the brain, and provide an example for each.

      5 For each of the following potential portals of entry, define key anatomical and/or physiological barriers that might prevent infection. (Select all that are appropriate.)Portals of EntrySting from an infected arthropodInhalation of virus-laden aerosol dropletsIngestion of virus-contaminated foodsExposure to semen from an infected maleKeratinized dead cell layerMucusLow pHBlood-brain barrier