Biology subjects

Perera, R. A. P. M.

Publications and source records attributed to Perera, R. A. P. M..

4 recordsLinked to original sources

bioRxiv2025

Clade C MERS-CoV camel strains vary in protease utilizationduring viral entry

MERS-CoV is a lethal pathogen with pandemic potential. Clade A and B MERS-CoV viruses have caused outbreaks in the Middle East since 2012 when they initially spilled over from camels to humans. Clade C viruses, however, are only found in camels across Africa and the spillover potential of these viruses seems to be lower than for clade A/B strains but remains to be fully understood. Here, we report that clade C spikes are less well-cleaved at the S1/S2 boundary than clade A or B viral spikes and that most clade C spikes induce reduced syncytium formation. Additionally, we demonstrate that several East African clade C strains are less able to utilize the TMPRSS2-mediated pathway for viral entry in both cell lines and primary nasal epithelial cultures. We map the molecular basis of this reduced TMPRSS2 usage to the N-terminal domain (NTD) and subdomain 2 (SD2) of East African clade C MERS-CoV. We suggest that reduced usage of the TMPRSS2-mediated entry pathway may underlie the reduced replication of East African clade C strains in humans, while the reduced replication of West African strains remains to be further investigated. Overall, we suggest that altered protease usage may contribute to differential tropism of East African clade C strains and indicate geographically distinct selection pressures on spike between MERS-CoV strains circulating in camels. Significance StatementClade A/B MERS-CoV outbreaks have caused 957 deaths since the first spillover in 2012; meanwhile, Clade C MERS-CoV strains have been found in camels across Africa but have not been reported to cause outbreaks. Investigating why these viruses do not successfully transmit to humans will be key to understanding the pandemic potential of the African MERS-CoV camel reservoir. Our study indicates that clade C viruses exhibit less spike cleavage and that East African clade C isolates are less able to utilize the TMPRSS2-mediated pathway during viral entry of both human cell lines and primary nasal cells. Differences in viral entry pathways could alter cellular and organ tropism and inform our understanding of the pandemic potential of these viruses.

microbiology↗

bioRxiv2020

Cross Sectional Study Of Middle East Respiratory Syndrome (MERS-CoV Infection) In Camels At Selected Sites Of Amibara District, Afar Region, Ethiopia

BackgroundA Cross sectional study of Middle East Respiratory Syndrome Corona virus (MERS-CoV) in Camel was conducted between February 2018 to April 2019 in three selected sites of Amibara district of Afar region, Northeast Ethiopia. The study was aimed to observe the current sero-prevalence status of MERS-CoV, assess the presence of active cases through detection RNA Viral particle and investigate possible risk factors of MERS-CoV in camels. A total of 589 sera were collected and tested with indirect Enzyme linked ImmunoSorbent Assay (iELISA). ResultThe overall seroprevalance of MERS-CoV was 87.3% (n=514/589, 95% CI: 84.5-89.9). Association of different risk factors with seroprevalance revealed that origin (X2=13.39,P=0.001), sex (X2=4.5 P=0.034), age ((X2=185.7, P=0.001) season (X2=41.7, P=0.000) and reproduction status (X2=96.1, P=0.001) displayed a statistical significant difference among the groups (P<0.05) while herd size did not show a Significant difference among groups (p>0.05). In multivariable logistic regression analysis, age (OR=7.39, 95% CI:3.43-15.91), season (OR=4.83, 95% CI:-2.14-10.90), and in adult female camel reproduction status (OR=7.39,95% C I:3.43-15.91) showed statistically significant difference among the groups for MERS CoV antibody detection while risk factors of origin, animal sex and herd size difference were statistically insignificant. A total of 857 nasal swab samples were collected for the detection of MERS-CoV RNA particle. However, all swab samples tested by Real-time reverse transcription polymerase chain reaction (RT-PCR) technique were Negative for the virus. ConclusionIn conclusion, the present study revealed a high seroprevalance of MERS CoV in adult camels. However, in spite of high seroprevalance the lack of any RNA viral particle in the study suggests the need for further in depth longitudinal study to detect the circulating virus focusing on juveniles and young camels whereby seroprevalance of antibody is low when compared with adult camel in order to get the active virus before the camel develop antibody. Moreover, the zoonotic significance and potential transmission routes of MERS CoV to pastoral communities should also be investigated and design strategy for the preparedness in control of the diseases in Ethiopia.

microbiology↗

bioRxiv2020

Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections

The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.

microbiology↗

bioRxiv2018

Age-specific differences in the dynamics of protective immunity to influenza

Influenza A viruses evolve rapidly to escape host immunity, such that individuals can be infected multiple times with the same subtype. The form and duration of protective immunity after each influenza infection are poorly understood. Here, we quantify the dynamics of protective immunity against influenza A virus infections by fitting individual-level mechanistic models to longitudinal serology from children and adults in a household cohort study. We find that most protection in children is explained by antibody titers measured by the hemagglutination inhibition (HI) assay. In contrast, in adults, HI antibody titers explain a smaller fraction of protection. Protection against circulating strains wanes to approximately 50% of peak levels 3.5-7 years after infection in both age groups, and wanes faster against influenza A(H3N2) than A(H1N1)pdm09. Protection against H3N2 lasts longer in adults than in children. Our results suggest that the focus of influenza antibody responses changes over time from the highly mutable hemagglutinin head to other epitopes, consistent with the immunological theory of original antigenic sin, and that this change of focus might affect protection. Additionally, we estimate that imprinting, or primary infection with a subtype of one phylogenetic group, has little to no effect on the risk of non-medically attended influenza infections in adults. We also find no evidence of long-term cross-protection between subtypes. This work underscores the need for longitudinal data on multiple components of the immune response to better understand the development of immunity and differences in susceptibility within populations.

epidemiology↗