scholarly journals Eilat Virus Host Range Restriction Is Present at Multiple Levels of the Virus Life Cycle

2014 ◽  
Vol 89 (2) ◽  
pp. 1404-1418 ◽  
Author(s):  
Farooq Nasar ◽  
Rodion V. Gorchakov ◽  
Robert B. Tesh ◽  
Scott C. Weaver
Keyword(s):  
Host Range ◽  
Nonstructural Protein ◽  
Rna Replication ◽  
Encephalitis Virus ◽  
Broad Host Range ◽  
Genomic Rna ◽  
Range Restriction ◽  
Entry Level ◽  
Equine Encephalitis Virus ◽  
Host Range Restriction

ABSTRACTMost alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates, including birds, rodents, equids, humans, and nonhuman primates. This ability of most alphaviruses to infect arthropods and vertebrates is essential for their maintenance in nature. Recently, a new alphavirus, Eilat virus (EILV), was described, and in contrast to all other mosquito-borne viruses, it is unable to replicate in vertebrate cell lines. Investigations into the nature of its host range restriction showed the inability of genomic EILV RNA to replicate in vertebrate cells. Here, we investigated whether the EILV host range restriction is present at the entry level and further explored the viral factors responsible for the lack of genomic RNA replication. Utilizing Sindbis virus (SINV) and EILV chimeras, we show that the EILV vertebrate host range restriction is also manifested at the entry level. Furthermore, the EILV RNA replication restriction is independent of the 3′ untranslated genome region (UTR). Complementation experiments with SINV suggested that RNA replication is restricted by the inability of the EILV nonstructural proteins to form functional replicative complexes. These data demonstrate that the EILV host range restriction is multigenic, involving at least one gene from both nonstructural protein (nsP) and structural protein (sP) open reading frames (ORFs). As EILV groups phylogenetically within the mosquito-borne virus clade of pathogenic alphaviruses, our findings have important evolutionary implications for arboviruses.IMPORTANCEOur work explores the nature of host range restriction of the first “mosquito-only alphavirus,” EILV. EILV is related to pathogenic mosquito-borne viruses (Eastern equine encephalitis virus [EEEV], Western equine encephalitis virus [WEEV], Venezuelan equine encephalitis virus [VEEV], and Chikungunya virus [CHIKV]) that cause severe disease in humans. Our data demonstrate that EILV is restricted both at entry and genomic RNA replication levels in vertebrate cells. These findings have important implications for arbovirus evolution and will help elucidate the viral factors responsible for the broad host range of pathogenic mosquito-borne alphaviruses, facilitate vaccine development, and inform potential strategies to reduce/prevent alphavirus transmission.

scholarly journals Analysis of Host Range Restriction Determinants in the Rabbit Model: Comparison of Homologous and Heterologous Rotavirus Infections

1998 ◽  
Vol 72 (3) ◽  
pp. 2341-2351 ◽  
Author(s):  
Max Ciarlet ◽  
Mary K. Estes ◽  
Christopher Barone ◽  
Robert F. Ramig ◽  
Margaret E. Conner
Keyword(s):  
Host Range ◽  
Model Comparison ◽  
Rabbit Model ◽  
Productive Infection ◽  
Complete Protection ◽  
Range Restriction ◽  
Rotavirus Infection ◽  
Replication Efficiency ◽  
Host Range Restriction ◽  
Rotavirus Infections

ABSTRACT The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV × D (G1), RRV × DS-1 (G2), and RRV × ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 103 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction. Also, our results suggest that VP4 may be involved in, but is not exclusively responsible for, host range restriction in the rabbit model. The replication efficiency of rotavirus in rabbits also is not controlled by the product of gene 5 (NSP1) alone, since a reassortant rotavirus with ALA gene 5 and all other genes from SA11 was more severely replication restricted than either parental rotavirus strain.

scholarly journals Host Range Restriction of Epstein-Barr Virus and Related Lymphocryptoviruses

2015 ◽  
Vol 89 (17) ◽  
pp. 9133-9136 ◽  
Author(s):  
Janine Mühe ◽  
Fred Wang
Keyword(s):  
B Cells ◽  
Host Range ◽  
Epstein Barr Virus ◽  
Nonhuman Primates ◽  
Range Restriction ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiple Species ◽  
High Degree ◽  
Host Range Restriction

Epstein-Barr-related herpesviruses, or lymphocryptoviruses (LCV), naturally infect humans and nonhuman primates (NHP), but their host range is not well characterized. Using LCV and B cells from multiple species of Hominidae and Cercopithecidae, we show that LCV can immortalize B cells from some nonnative species but that growth transformation is restricted to B cells from their own family of hominoids or Old World NHP, suggesting a high degree of LCV adaptation to their natural primate host.

scholarly journals Determinants of the Host Range Restriction of Replication of Bovine Parainfluenza Virus Type 3 in Rhesus Monkeys Are Polygenic

2003 ◽  
Vol 77 (2) ◽  
pp. 1141-1148 ◽  
Author(s):  
Mario H. Skiadopoulos ◽  
Alexander C. Schmidt ◽  
Jeffrey M. Riggs ◽  
Sonja R. Surman ◽  
William R. Elkins ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Host Range ◽  
Rhesus Monkeys ◽  
Single Unit ◽  
Parainfluenza Virus ◽  
Wild Type ◽  
Range Restriction ◽  
Type 3 ◽  
Bovine Parainfluenza Virus ◽  
Host Range Restriction

ABSTRACT The Kansas strain of bovine parainfluenza virus type 3 (BPIV3) is 100- to 1,000-fold restricted in replication in the respiratory tracts of nonhuman primates compared to human PIV3 (HPIV3), an important pathogen of infants and young children. BPIV3 is also restricted in replication in human infants and children, yet it is immunogenic and is currently being evaluated in clinical trials as a vaccine candidate to protect against illness caused by HPIV3. We have examined the genetic basis for the host range attenuation phenotype of BPIV3 by exchanging each open reading frame (ORF) of a recombinant wild-type HPIV3 with the analogous ORF from BPIV3, with the caveats that the multiple ORFs of the P gene were exchanged as a single unit and that the HN and F genes were exchanged as a single unit. Recombinant chimeric bovine-human PIV3s were recovered from cDNA, and the levels of viral replication in vitro and in the respiratory tract of rhesus monkeys were determined. Recombinant chimeric HPIV3s bearing the BPIV3 N or P ORF were highly attenuated in the upper and lower respiratory tracts of monkeys, whereas those bearing the BPIV3 M or L ORF or the F and HN genes were only moderately attenuated. This indicates that the genetic determinants of the host range restriction of replication of BPIV3 for primates are polygenic, with the major determinants being the N and P ORFs. Monkeys immunized with these bovine-human chimeric viruses, including the more highly attenuated ones, developed higher levels of HPIV3 hemagglutination-inhibiting serum antibodies than did monkeys immunized with BPIV3 and were protected from challenge with wild-type HPIV3. Furthermore, host range determinants could be combined with attenuating point mutations to achieve an increased level of attenuation. Thus, chimeric recombinant bovine-human PIV3 viruses that manifest different levels of attenuation in rhesus monkeys are available for evaluation as vaccine candidates to protect infants from the severe lower respiratory tract disease caused by HPIV3.

scholarly journals Newcastle Disease Virus V Protein Is a Determinant of Host Range Restriction

2003 ◽  
Vol 77 (17) ◽  
pp. 9522-9532 ◽  
Author(s):  
Man-Seong Park ◽  
Adolfo García-Sastre ◽  
Jerome F. Cros ◽  
Christopher F. Basler ◽  
Peter Palese
Keyword(s):  
Newcastle Disease Virus ◽  
Host Range ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Range Restriction ◽  
V Protein ◽  
Species Specific ◽  
Chicken Eggs ◽  
Host Range Restriction ◽  
Embryonated Chicken

ABSTRACT It has been demonstrated that the V protein of Newcastle disease virus (NDV) functions as an alpha/beta interferon (IFN-α/β) antagonist (M. S. Park, M. L. Shaw, J. Muñoz-Jordan, J. F. Cros, T. Nakaya, N. Bouvier, P. Palese, A. García-Sastre, and C. F. Basler, J. Virol. 77:1501-1511, 2003). We now show that the NDV V protein plays an important role in host range restriction. In order to study V functions in vivo, recombinant NDV (rNDV) mutants, defective in the expression of the V protein, were generated. These rNDV mutants grow poorly in both embryonated chicken eggs and chicken embryo fibroblasts (CEFs) compared to the wild-type (wt) rNDV. However, insertion of the NS1 gene of influenza virus A/PR8/34 into the NDV V(−) genome [rNDV V(−)/NS1] restores impaired growth to wt levels in embryonated chicken eggs and CEFs. These data indicate that for viruses infecting avian cells, the NDV V protein and the influenza NS1 protein are functionally interchangeable, even though there are no sequence similarities between the two proteins. Interestingly, in human cells, the titer of wt rNDV is 10 times lower than that of rNDV V(−)/NS1. Correspondingly, the level of IFN secreted by human cells infected with wt rNDV is much higher than that secreted by cells infected with the NS1-expressing rNDV. This suggests that the IFN antagonist activity of the NDV V protein is species specific. Finally, the NDV V protein plays an important role in preventing apoptosis in a species-specific manner. The rNDV defective in V induces apoptotic cell death more rapidly in CEFs than does wt rNDV. Taken together, these data suggest that the host range of NDV is limited by the ability of its V protein to efficiently prevent innate host defenses, such as the IFN response and apoptosis.

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