Transcription enhancers as major determinants of SV40 polyomavirus growth efficiency and host cell tropism

ABSTRACT Toxoplasma gondii is an obligate intracellular protozoan parasite that invades and replicates within most nucleated cells of warm-blooded animals. The basis for this wide host cell tropism is unknown but could be because parasites invade host cells using distinct pathways and/or repertoires of host factors. Using synchronized parasite invasion assays, we found that host microtubule disruption significantly reduces parasite invasion into host cells early after stimulating parasite invasion but not at later time points. Host microtubules are specifically associated with the moving junction, which is the site of contact between the host cell and the invading parasite. Host microtubules are specifically associated with the moving junction of those parasites invading early after stimulating invasion but not with those invading later. Disruption of host microtubules has no effect on parasite contact, attachment, motility, or rate of penetration. Rather, host microtubules hasten the time before parasites commence invasion. This effect on parasite invasion is distinct from the role that host microtubules play in bacterial and viral infections, where they function to traffic the pathogen or pathogen-derived material from the host cell's periphery to its interior. These data indicate that the host microtubule cytoskeleton is a structure used by Toxoplasma to rapidly infect its host cell and highlight a novel function for host microtubules in microbial pathogenesis.

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Replication-competent chimeric lenti-oncovirus with expanded host cell tropism.

Journal of Virology ◽

10.1128/jvi.71.4.3328-3331.1997 ◽

1997 ◽

Vol 71 (4) ◽

pp. 3328-3331 ◽

Cited By ~ 15

Author(s):

S Reiprich ◽

B R Gundlach ◽

B Fleckenstein ◽

K Uberla

Keyword(s):

Host Cell ◽

Cell Tropism

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Expansion of host-cell tropism of foot-and-mouth disease virus despite replication in a constant environment

Journal of General Virology ◽

10.1099/vir.0.80126-0 ◽

2004 ◽

Vol 85 (8) ◽

pp. 2289-2297 ◽

Cited By ~ 26

Author(s):

Carmen M. Ruiz-Jarabo ◽

Nonia Pariente ◽

Eric Baranowski ◽

Mercedes Dávila ◽

Gema Gómez-Mariano ◽

...

Keyword(s):

Host Cell ◽

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Jurkat Cells ◽

Virus Infectivity ◽

Cell Tropism ◽

Cellular Environment ◽

Mouth Disease Virus ◽

Foot And Mouth

Foot-and-mouth disease virus (FMDV) variants adapted to BHK-21 cells showed an expanded host-cell tropism that extended to primate and human cell lines. Virus replication in human HeLa and Jurkat cells has been documented by titration of virus infectivity, quantification of virus RNA, expression of a virus-specific non-structural antigen, and serial passage of virus in the cells. Parallel serial infections of human Jurkat cells with the same variant FMDVs indicates a strong stochastic component in the progression of infection. Chimeric viruses identified the capsid as a genomic region involved in tropism expansion. These results indicate that, contrary to theoretical predictions, replication of an RNA virus in a constant cellular environment may lead to expansion of cellular tropism, rather than to a more specialized infection of the cellular type to which the virus has been adapted.

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Substitutions at the Putative Receptor-Binding Site of an Encephalitic Flavivirus Alter Virulence and Host Cell Tropism and Reveal a Role for Glycosaminoglycans in Entry

Journal of Virology ◽

10.1128/jvi.74.19.8867-8875.2000 ◽

2000 ◽

Vol 74 (19) ◽

pp. 8867-8875 ◽

Cited By ~ 107

Author(s):

Eva Lee ◽

Mario Lobigs

Keyword(s):

Host Cell ◽

Receptor Binding ◽

Mammalian Cells ◽

Virus Entry ◽

Single Amino Acid ◽

Binding Motif ◽

Virus Infectivity ◽

Cell Tropism ◽

E Protein ◽

The Impact

ABSTRACT The flavivirus receptor-binding domain has been putatively assigned to a hydrophilic region (FG loop) in the envelope (E) protein. In some flaviviruses this domain harbors the integrin-binding motif Arg-Gly-Asp (RGD). One of us has shown earlier that host cell adaptation of Murray Valley encephalitis virus (MVE) can result in the selection of attenuated variants altered at E protein residue Asp390, which is part of an RGD motif. Here, a full-length, infectious cDNA clone of MVE was constructed and employed to systematically investigate the impact of single amino acid changes at Asp390 on cell tropism, virus entry, and virulence. Each of 10 different E protein 390 mutants was viable. Three mutants (Gly390, Ala390, and His390) showed pronounced differences from an infectious clone-derived control virus in growth in mammalian and mosquito cells. The altered cell tropism correlated with (i) a difference in entry kinetics, (ii) an increased dependence on glycosaminoglycans (determined by inhibition of virus infectivity by heparin) for attachment of the three mutants to different mammalian cells, and (iii) the loss of virulence in mice. These results confirm a functional role of the FG loop in the flavivirus E protein in virus entry and suggest that encephalitic flaviviruses can enter cells via attachment to glycosaminoglycans. However, it appears that additional cell surface molecules are also used as receptors by natural isolates of MVE and that the increased dependence on glycosaminoglycans for entry results in the loss of neuroinvasiveness.

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Variation of Host Cell Tropism of Porcine Endogenous Retroviruses Expressed in Chinese Banna Minipig Inbred

Intervirology ◽

10.1159/000090787 ◽

2006 ◽

Vol 49 (4) ◽

pp. 185-191 ◽

Cited By ~ 3

Author(s):

Zhang Li ◽

Yu Ping ◽

Li Shengfu ◽

Zeng Yangzhi ◽

Cheng Jingqiu ◽

...

Keyword(s):

Host Cell ◽

Endogenous Retroviruses ◽

Cell Tropism ◽

Porcine Endogenous Retroviruses

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Selection Pressure in the Human Adenovirus Fiber Knob Drives Cell Specificity in Epidemic Keratoconjunctivitis

Journal of Virology ◽

10.1128/jvi.01010-16 ◽

2016 ◽

Vol 90 (21) ◽

pp. 9598-9607 ◽

Cited By ~ 11

Author(s):

Ashrafali M. Ismail ◽

Ji Sun Lee ◽

David W. Dyer ◽

Donald Seto ◽

Jaya Rajaiya ◽

...

Keyword(s):

Amino Acid ◽

Host Cell ◽

Ocular Surface ◽

Hot Spot ◽

Human Adenovirus ◽

Host Cells ◽

Survival Strategies ◽

Corneal Epithelial Cell ◽

Cell Tropism ◽

Epidemic Keratoconjunctivitis

ABSTRACTHuman adenoviruses (HAdVs) contain seven species (HAdV-A to -G), each associated with specific disease conditions. Among these, HAdV-D includes those viruses associated with epidemic keratoconjunctivitis (EKC), a severe ocular surface infection. The reasons for corneal tropism for some but not all HAdV-Ds are not known. The fiber protein is a major capsid protein; its C-terminal “knob” mediates binding with host cell receptors to facilitate subsequent viral entry. In a comprehensive phylogenetic analysis of HAdV-D capsid genes, fiber knob gene sequences of HAdV-D types associated with EKC formed a unique clade. By proteotyping analysis, EKC virus-associated fiber knobs were uniquely shared. Comparative structural modeling showed no distinct variations in fiber knobs of EKC types but did show variation among HAdV-Ds in a region overlapping with the known CD46 binding site in HAdV-B. We also found signature amino acid positions that distinguish EKC from non-EKC types, and byin vitrostudies we showed that corneal epithelial cell tropism can be predicted by the presence of a lysine or alanine at residue 240. This same amino acid residue in EKC viruses shows evidence for positive selection, suggesting that evolutionary pressure enhances fitness in corneal infection, and may be a molecular determinant in EKC pathogenesis.IMPORTANCEViruses adapt various survival strategies to gain entry into target host cells. Human adenovirus (HAdV) types are associated with distinct disease conditions, yet evidence for connections between genotype and cellular tropism is generally lacking. Here, we provide a structural and evolutionary basis for the association between specific genotypes within HAdV species D and epidemic keratoconjunctivitis, a severe ocular surface infection. We find that HAdV-D fiber genes of major EKC pathogens, specifically the fiber knob gene region, share a distinct phylogenetic clade. Deeper analysis of the fiber gene revealed that evolutionary pressure at crucial amino acid sites has a significant impact on its structural conformation, which is likely important in host cell binding and entry. Specific amino acids in hot spot residues provide a link to ocular cell tropism and possibly to corneal pathogenesis.

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Feline and Canine Coronaviruses: Common Genetic and Pathobiological Features

Advances in Virology ◽

10.1155/2011/609465 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

Sophie Le Poder

Keyword(s):

Infectious Disease ◽

Severe Acute Respiratory Syndrome ◽

Host Cell ◽

Companion Animals ◽

Cell Tropism ◽

Human Coronavirus ◽

Feline Infectious Peritonitis ◽

Canine Coronavirus ◽

Coronavirus Infection ◽

Systemic Infections

A new human coronavirus responsible for severe acute respiratory syndrome (SARS) was identified in 2003, which raised concern about coronaviruses as agents of serious infectious disease. Nevertheless, coronaviruses have been known for about 50 years to be major agents of respiratory, enteric, or systemic infections of domestic and companion animals. Feline and canine coronaviruses are widespread among dog and cat populations, sometimes leading to the fatal diseases known as feline infectious peritonitis (FIP) and pantropic canine coronavirus infection in cats and dogs, respectively. In this paper, different aspects of the genetics, host cell tropism, and pathogenesis of the feline and canine coronaviruses (FCoV and CCoV) will be discussed, with a view to illustrating how study of FCoVs and CCoVs can improve our general understanding of the pathobiology of coronaviruses.

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