Asha Ann Philip

• BVSc &AH, MVSc (Veterinary Pathology), Ph.D. in Microbiology (Virology)
• Investigator I at CSL Seqirus

Viruses engage in a variety of processes to subvert host defenses and create an environment amenable to replication. Here, using rotavirus as a prototype, we show that calcium conductance out of the endoplasmic reticulum by the virus encoded ion channel, NSP4 , induces intercellular calcium waves that extend beyond the infected cell and contribute...

Acute gastroenteritis remains the second leading cause of death among children under the age of 5 worldwide. While enteric viruses are the most common etiology, the drivers of their virulence remain incompletely understood. We recently found that cells infected with rotavirus, the most prevalent enteric virus in infants and young children, initiate...

Rotaviruses are the primary cause of severe gastroenteritis in infants and young children throughout the world. To combat rotavirus illness, several live oral vaccines have been developed, or are under development, that are formulated from attenuated human or human–animal reassortant strains of rotavirus. While the effectiveness of these vaccines i...

Reverse genetic systems have been used to introduce heterologous sequences into the rotavirus segmented double-stranded (ds)RNA genome, enabling the generation of recombinant viruses that express foreign proteins and possibly serve as vaccine vectors. Notably, insertion of SARS-CoV-2 sequences into the segment seven (NSP3) RNA of simian SA11 rotavi...

The live oral rotavirus RV1 (Rotarix) vaccine is formulated from the human G1P[8] RIX4414 virus. Based on RIX4414 sequences, T7 expression plasmids were constructed that supported recovery of recombinant RIX4414-like viruses by reverse genetics. These plasmids will advance the study of the RV1 vaccine, possibly allowing improvements to its efficacy...

For productive infection, rotavirus and other RNA viruses must suppress interferon (IFN) signaling and the expression of IFN-stimulated antiviral gene products. Particularly important is inhibiting the interferon (IFN)-inducible 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway, as activated RNase L can direct the nonspecific degradation of vir...

Rotavirus, a segmented double-stranded RNA virus of the Reoviridae family, is a primary cause of acute gastroenteritis in young children. In countries where rotavirus vaccines are widely used, norovirus (NoV) has emerged as the major cause of acute gastroenteritis. Towards the goal of creating a combined rotavirus-NoV vaccine, we explored the possi...

The interferon (IFN)-inducible 2′,5′-oligoadenylate synthetase (OAS) - RNase L pathway plays a critical role in antiviral immunity. Group A rotaviruses, including the simian SA11 strain, inhibit this pathway through two activities: an E3-ligase related activity of NSP1 that degrades proteins necessary for IFN signaling, and a phosphodiesterase (PDE...

Rotaviruses, segmented dsRNA viruses of the Reoviridae family, are a primary cause of acute gastroenteritis in young children. In countries where rotavirus vaccines are widely used, norovirus (NoV) has emerged as the major cause of acute gastroenteritis. Towards the goal of creating a combined rotavirus-NoV vaccine, we explored the possibility of g...

Among vaccines administered to children are those targeting rotavirus, a segmented double-stranded RNA virus that represents a major cause of severe gastroenteritis. To explore the feasibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotaviruses with modified segment 7 RNAs that contained coding cass...

Rotavirus, a segmented double-stranded RNA virus, is a major cause of acute gastroenteritis in young children. The introduction of live oral rotavirus vaccines has reduced the incidence of rotavirus disease in many countries. To explore the possibility of establishing a combined rotavirus-SARS-CoV-2 vaccine, we generated recombinant (r)SA11 rotavir...

Rotaviruses are a major cause of severe gastroenteritis in infants and young children. Recently, a highly efficient reverse genetics system was developed that allows genetic manipulation of the rotavirus segmented double-stranded RNA genome. Using the reverse genetics system, we show that it is possible to modify one of the rotavirus genome segment...

Although the incidence of rotavirus diarrheal disease has been reduced by the introduction of neonatal rotavirus vaccines, other enteric viruses—including norovirus, hepatitis E virus (HEV), and astrovirus—remain significant causes of illness. In this study, we investigated the possibility of generating recombinant rotaviruses that express the caps...

The segmented 18.5-kB dsRNA genome of rotavirus expresses 6 structural and 6 nonstructural proteins. We investigated the possibility of using the recently-developed plasmid-based rotavirus reverse genetics (RG) system to generate recombinant viruses that express a separate foreign protein, in addition to the 12 viral proteins. To address this, we r...

Previous studies generated recombinant rotaviruses that express FPs by inserting reporter genes into the NSP1 ORF of genome segment 5. Unfortunately, NSP1 is expressed at low levels in infected cells, making viruses expressing FP-fused NSP1 less than ideal probes of rotavirus biology. Moreover, FPs were inserted into segment 5 in such a way as to c...

Rotavirus reverse genetics: a step by sept protocol

Like many viruses, rotavirus (RV) dysregulates calcium homeostasis by elevating cytosolic calcium ([Ca2+]cyt) and decreasing endoplasmic reticulum (ER) stores. While an overall, monophasic increase in [Ca2+]cyt during RV infection has been shown, the nature of the RV-induced aberrant calcium signals and how they manifest over time at the single-cel...

A collection of recombinant rotaviruses that express the fluorescent markers UnaG, mKate, mRuby, TagBFP, CFP, or YFP as separate proteins was generated. Genes for the fluorescent proteins were inserted into genome segment 7 without compromising expression of the protein NSP3. These recombinant rotaviruses are valuable for analyzing rotavirus biolog...

Rotavirus is a segmented double-stranded (ds)RNA virus that causes severe gastroenteritis in young children. We have established an efficient simplified rotavirus reverse genetics (RG) system that uses eleven T7 plasmids, each expressing a unique simian SA11 (+)RNA, and a CMV support plasmid for the African swine fever virus NP868R capping enzyme....

Like many viruses, rotavirus (RV) dysregulates calcium homeostasis by elevating cytosolic calcium and decreasing endoplasmic reticulum (ER) stores. While an overall, monophasic increase in cytosolic calcium during RV infection has been shown, the nature of the RV-induced aberrant calcium signals and how they manifest over time at the single-cell le...

Recently, Kanai and his colleagues developed an all plasmid-based reverse genetics (RG) system for SA11 rotavirus. The system consists of eleven T7-transcription plasmids, each expressing a unique SA11 (+)RNA, and three CMV support plasmids, one expressing an avian reovirus fusogenic FAST protein, and the other two expressing the vaccinia virus D1R...

Present paper describes a rare case of cutaneous capillary haemangioma in a white Pekin duck (Anas platyrhinchos domesticus). Grossly, tumour mass was of 5 cm in diameter, soft, reddish, ulcerated and localized near the axilla of left hind limb. Histological examination revealed thickened dermis and variable sized blood filled vascular lumina, nume...

Canine perianal adenocarcinoma is a malignant tumourthat occurs mainly in old dogs and arises from the modified sebaceous perianal glands, often referred to as ‘‘hepatoid glands’’ because of their morphological resemblance to hepatocytes. The present communication reports a perianal gland carcinoma with metastases to various organs. ALabrador bitch...